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Szeliski K, Fekner Z, Kasiński D, Rasmus M, Kowalski F, Świtońska M, Sierakowska K, Drewa T, Pokrywczyńska M. The potential of plasma-derived medium-sized extracellular vesicles as a biopsy alternative for active surveillance decisions in prostate Cancer. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2025; 67:102828. [PMID: 40360098 DOI: 10.1016/j.nano.2025.102828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 04/18/2025] [Accepted: 05/09/2025] [Indexed: 05/15/2025]
Abstract
Diagnosing prostate cancer (PCa) and risk-stratifying patients remains challenging, as PSA-based methods lack precision for active surveillance (AS) decision-making. Extracellular vesicles (EVs) are membranous nano-sized vesicles released by all types of cells and may contain potentially interesting material for diagnostic procedures for PCa. This study analyzed surface markers and miRNA profiles of medium-sized plasma EVs (mEVs) from 24 PCa patients using nanoflow cytometry and miRNA profiling. The ratio of PSMA+ EVs to PSMA+CD9+ EVs differed significantly between AS and non-AS patients. Additionally, miR-99a-5p, miR-125b-5p, miR-145-5p, and miR-365a-3p levels were higher in non-AS patients. These findings suggest that plasma-derived PSMA+ mEVs originate from the prostate and may serve as biomarkers for PCa progression. Nanoflow cytometry-based analysis of EV surface markers combined with miRNA profiling provides a novel, non-invasive alternative to PSA measurements. This approach could improve risk stratification and decision-making for AS patients, potentially leading to better outcomes.
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Affiliation(s)
- Kamil Szeliski
- Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland.
| | - Zuzanna Fekner
- Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Damian Kasiński
- Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Marta Rasmus
- Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Filip Kowalski
- Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Milena Świtońska
- Department of Neurology and Clinical Neurophysiology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Katarzyna Sierakowska
- Faculty of Medicine, Bydgoszcz University of Science and Technology, Bydgoszcz, Poland
| | - Tomasz Drewa
- Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Marta Pokrywczyńska
- Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
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Delshad M, Sanaei MJ, Mohammadi MH, Sadeghi A, Bashash D. Exosomal Biomarkers: A Comprehensive Overview of Diagnostic and Prognostic Applications in Malignant and Non-Malignant Disorders. Biomolecules 2025; 15:587. [PMID: 40305328 PMCID: PMC12024574 DOI: 10.3390/biom15040587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 04/07/2025] [Accepted: 04/09/2025] [Indexed: 05/02/2025] Open
Abstract
Exosomes are small extracellular vesicles, ranging from 30 to 150 nm, that are essential in cell biology, mediating intercellular communication and serving as biomarkers due to their origin from cells. Exosomes as biomarkers for diagnosing various illnesses have gained significant investigation due to the high cost and invasive nature of current diagnostic procedures. Exosomes have a clear advantage in the diagnosis of diseases because they include certain signals that are indicative of the genetic and proteomic profile of the ailment. This feature gives them the potential to be useful liquid biopsies for real-time, noninvasive monitoring, enabling early cancer identification for the creation of individualized treatment plans. According to our analysis, the trend toward utilizing exosomes as diagnostic and prognostic tools has raised since 2012. In this regard, the proportion of malignant indications is higher compared with non-malignant ones. To be precise, exosomes have been used the most in gastrointestinal, thoracic, and urogenital cancers, along with cardiovascular, diabetic, breathing, infectious, and brain disorders. To the best of our knowledge, this is the first research to examine all registered clinical trials that look at exosomes as a diagnostic and prognostic biomarker.
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Affiliation(s)
- Mahda Delshad
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
- Department of Laboratory Sciences, School of Allied Medical Sciences, Zanjan University of Medical Sciences, Zanjan 1411718541, Iran
| | - Mohammad-Javad Sanaei
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
| | - Mohammad Hossein Mohammadi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
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Boucher J, Pépin G, Goyer B, Hubert A, Bazié WW, Vitry J, Barabé F, Gilbert C. Exploring the relationship between extracellular vesicles, the dendritic cell immunoreceptor, and microRNA-155 in an in vivo model of HIV-1 infection to understand the disease and develop new treatments. FASEB J 2025; 39:e70475. [PMID: 40111214 DOI: 10.1096/fj.202402692rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 03/05/2025] [Accepted: 03/11/2025] [Indexed: 03/22/2025]
Abstract
HIV-1 infection induces persistent immune system activation despite antiretroviral therapy. New immunomodulatory targets might be required to restore immune competence. The dendritic cells immunoreceptor (DCIR) can bind HIV-1 and regulate immune functions and extracellular vesicles (EVs) production. EVs have emerged as biomarkers and a non-invasive tool to monitor HIV-1 progression. In people living with HIV-1, an increase in the size and abundance of EVs is associated with a decline in the CD4/CD8 T cells ratio, a key marker of immune dysfunction. Analysis of host nucleic acids within EVs has revealed an enrichment of microRNA-155 (miR-155) during HIV-1 infection. Experiments have demonstrated that miR-155-rich EVs enhance HIV-1 infection in vitro. A humanized NSG-mouse model was established to assess the in vivo impact of miR-155-rich EVs. Co-production of the virus with miR-155-rich EVs heightened the viral load and lowered the CD4/CD8 ratio in the mice. Upon euthanasia, EVs were isolated from plasma for size and quantity assessment. Consistent with findings in individuals with HIV-1, increased EV size and abundance were inversely correlated with the CD4/CD8 ratio. Next, by using the virus co-product with EV-miR-155, we tested a DCIR inhibitor to limit infection and immune damage in a humanized mouse model. DCIR inhibition reduced infection and partially restored immune functions. Finally, viral particles and various EV subtypes can convey HIV-1 RNA. HIV-1 RNA was predominantly associated with large EVs (200-1000 nm) rather than small EVs (50-200 nm). Viral loads in large EVs strongly correlated with blood and tissue markers of immune activation. The humanized mice model has proven its applicability to studying the roles of EVs on HIV-1 infection and investigating the impact of DCIR inhibition.
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Affiliation(s)
- Julien Boucher
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
| | - Gabriel Pépin
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
| | - Benjamin Goyer
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
| | - Audrey Hubert
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
| | - Wilfried Wenceslas Bazié
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Programme de Recherche Sur les Maladies Infectieuses, Centre Muraz, Institut National de Santé Publique, Bobo-Dioulasso, Burkina Faso
| | - Julien Vitry
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
| | - Frédéric Barabé
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Département de médecine, Faculté de médecine, Université Laval, Québec, Quebec, Canada
| | - Caroline Gilbert
- Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
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Hamid Y, Rabbani RD, Afsara R, Nowrin S, Ghose A, Papadopoulos V, Sirlantzis K, Ovsepian SV, Boussios S. Exosomal Liquid Biopsy in Prostate Cancer: A Systematic Review of Biomarkers for Diagnosis, Prognosis, and Treatment Response. Int J Mol Sci 2025; 26:802. [PMID: 39859516 PMCID: PMC11765602 DOI: 10.3390/ijms26020802] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 01/15/2025] [Accepted: 01/17/2025] [Indexed: 01/27/2025] Open
Abstract
Prostate cancer, a leading cause of cancer-related mortality among men, often presents challenges in accurate diagnosis and effective monitoring. This systematic review explores the potential of exosomal biomolecules as noninvasive biomarkers for the diagnosis, prognosis, and treatment response of prostate cancer. A thorough systematic literature search through online public databases (Medline via PubMed, Scopus, and Web of science) using structured search terms and screening using predefined eligibility criteria resulted in 137 studies that we analyzed in this systematic review. We evaluated the findings from these clinical studies, revealing that the load of exosomes in the blood and urine of prostate cancer patients, which includes microRNAs (miRNAs), proteins, and lipids, demonstrates disease-specific changes. It also shows that some exosomal markers can differentiate between malignant and benign hyperplasia of the prostate, predict disease aggressiveness, and monitor treatment efficacy. Notably, miRNA emerged as the most frequently studied biomolecule, demonstrating superior diagnostic potential compared to traditional methods like prostate-specific antigen (PSA) testing. The analysis also highlights the pressing need for a standardised analytic approach through multi-centre studies to validate the full potential of exosomal biomarkers for the diagnosis and monitoring of prostate cancer.
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Affiliation(s)
- Yameen Hamid
- The University of Edinburgh, Edinburgh EH8 9YL, UK;
- Department of Acute Medicine, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Rukhshana Dina Rabbani
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK; (R.D.R.); (A.G.)
| | - Rakkan Afsara
- Department of Medical Oncology, Evercare Hospital, Dhaka 1205, Bangladesh;
| | - Samarea Nowrin
- Department of Clinical Oncology, Maidstone and Tunbridge Wells NHS Trust, Maidstone ME16 9QQ, UK;
| | - Aruni Ghose
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK; (R.D.R.); (A.G.)
| | | | - Konstantinos Sirlantzis
- School of Engineering, Technology and Design, Canterbury Christ Church University, Canterbury CT1 1QU, UK;
| | - Saak V. Ovsepian
- Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime, Kent ME4 4TB, UK;
- Faculty of Medicine, Tbilisi State University, Tbilisi 0177, Georgia
| | - Stergios Boussios
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK; (R.D.R.); (A.G.)
- Faculty of Medicine, Health, and Social Care, Canterbury Christ Church University, Canterbury CT2 7PB, UK
- School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King’s College London, Strand, London WC2R 2LS, UK
- Kent and Medway Medical School, University of Kent, Canterbury CT2 7LX, UK
- AELIA Organisation, 9th km Thessaloniki—Thermi, 57001 Thessaloniki, Greece
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Špilak A, Brachner A, Friedl HP, Klepe A, Nöhammer C, Neuhaus W. Effects of small extracellular vesicles derived from normoxia- and hypoxia-treated prostate cancer cells on the submandibular salivary gland epithelium in vitro. Tissue Barriers 2025; 13:2347062. [PMID: 38721756 PMCID: PMC11875469 DOI: 10.1080/21688370.2024.2347062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 04/18/2024] [Accepted: 04/18/2024] [Indexed: 03/03/2025] Open
Abstract
Small extracellular vesicles (sEVs) are an important part of intercellular communication. They are phospholipid bilayer particles that carry active biomolecules such as proteins, various nucleic acids, and lipids. In recipient cells, sEVs can alter cellular functions, including cancer development and premetastatic niche formation in distant organs. Moreover, sEVs can carry cancer-specific features, which makes them promising biomarker candidates. However, the interactions of sEVs with biological barriers and consequences thereof, are not clarified yet. The blood-saliva barrier is crucial for preventing the entry of pathogens and (in)organic substances into the bloodstream, as well as molecule filtration from blood to saliva. The effects of brain derived DU145 prostate cancer (PCa) sEVs on a human submandibular salivary gland barrier (SSGB) in vitro were investigated. Small EVs were harvested from normoxic (N, atmospheric O2) or hypoxic (H, 1% O2) conditions, fluorescently labeled with CellTrackerTM Orange and thoroughly characterized. HTB-41 B2 cells were used as SSGB model cultured on 24-well ThinCert® inserts. After model optimization indicating effects of serum and serum-sEVs on barrier properties, PCa sEVs were applied to the basolateral (blood) side in either 10% serum, or serum-free conditions, and barrier integrity was continuously monitored for 40 hours. This study found that H and N PCa sEVs were uptaken by the SSGB in vitro model in similar quantities regardless of the media composition in the basolateral compartment. Permeation of fluorescent PCa sEVs into the apical compartment was not detectable with the applied methods. However, treatment with H and N sEVs under different serum conditions revealed distinct molecular clusters after hierarchical analysis of mRNA data measured by high-throughput qPCR, which were partly reflected at the protein level. For example, serum-reduction dependent decrease of barrier properties was accompanied with the decrease of CDH1 or Claudin-7 expression. Interestingly, the presence of H sEVs significantly increased the number of sEV-sized particles in the apical compartment of the SSGB model compared to basolaterally added N sEVs. This functional effect on the number of particles in the saliva (apical) compartment induced by different sEVs applied in the blood (basolateral) compartment might be a new approach to understand one possible mechanism how differences of salivary EVs might occur which then could be used as biomarker.
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Affiliation(s)
- Ana Špilak
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT - Austrian Institute of Technology GmbH, Vienna, Austria
| | - Andreas Brachner
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT - Austrian Institute of Technology GmbH, Vienna, Austria
| | - Heinz-Peter Friedl
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT - Austrian Institute of Technology GmbH, Vienna, Austria
| | - Adrián Klepe
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT - Austrian Institute of Technology GmbH, Vienna, Austria
| | - Christa Nöhammer
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT - Austrian Institute of Technology GmbH, Vienna, Austria
| | - Winfried Neuhaus
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT - Austrian Institute of Technology GmbH, Vienna, Austria
- Faculty of Medicine and Dentistry, Danube Private University, Krems, Austria
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Wang Q, Pang B, Bucci J, Jiang J, Li Y. The emerging role of extracellular vesicles and particles in prostate cancer diagnosis, and risk stratification. Biochim Biophys Acta Rev Cancer 2024; 1879:189210. [PMID: 39510450 DOI: 10.1016/j.bbcan.2024.189210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 10/29/2024] [Accepted: 10/31/2024] [Indexed: 11/15/2024]
Abstract
Current approaches for prostate cancer (PCa) diagnosis and risk stratification require greater accuracy. Extracellular vesicles and particles (EVPs) containing diverse cargos from parent cells are released into the extracellular microenvironment and play a critical role in intercellular communication. Accumulating evidence demonstrates that EVPs are emerging as a promising focus for the exploration of cancer biomarkers and therapeutic targets. However, the precise categorisation and nomenclature of EVP subpopulations remains challenging due to their compositional complexity, inherent heterogeneity in molecular composition, and structure. The recent identification of two novel non-vesicular extracellular particle subtypes, exomeres and supermeres, has altered our understanding of the distinct subpopulations of EVPs and their roles in biological and physiological processes. Here, we discuss recent advances in the field of EVPs, describe characteristics of EVP subpopulations, focus on the application and potential of EVPs in PCa diagnosis and risk stratification by liquid biopsy, and highlight the major challenges and prospects of EVP research in PCa area.
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Affiliation(s)
- Qi Wang
- St. George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Sydney, Kensington, NSW 2052, Australia; Cancer Care Centre, St. George Hospital, Kogarah, NSW 2217, Australia
| | - Bairen Pang
- Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Ningbo Clinical Research Centre for Urological Disease, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Translational Research Laboratory for Urology, The Key Laboratory of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Zhejiang Engineering Research Centre of Innovative Technologies and Diagnostic and Therapeutic Equipment for Urinary System Diseases, Ningbo, Zhejiang 315010, China
| | - Joseph Bucci
- St. George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Sydney, Kensington, NSW 2052, Australia; Cancer Care Centre, St. George Hospital, Kogarah, NSW 2217, Australia
| | - Junhui Jiang
- Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Ningbo Clinical Research Centre for Urological Disease, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Translational Research Laboratory for Urology, The Key Laboratory of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Zhejiang Engineering Research Centre of Innovative Technologies and Diagnostic and Therapeutic Equipment for Urinary System Diseases, Ningbo, Zhejiang 315010, China.
| | - Yong Li
- St. George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Sydney, Kensington, NSW 2052, Australia; Cancer Care Centre, St. George Hospital, Kogarah, NSW 2217, Australia.
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Wang X, Zhang L, Cheng L, Wang Y, Li M, Yu J, Ma Z, Ho PCL, Sethi G, Chen X, Wang L, Goh BC. Extracellular vesicle-derived biomarkers in prostate cancer care: Opportunities and challenges. Cancer Lett 2024; 601:217184. [PMID: 39142499 DOI: 10.1016/j.canlet.2024.217184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/04/2024] [Accepted: 08/07/2024] [Indexed: 08/16/2024]
Abstract
Prostate cancer (PCa) is the second most prevalent cancer in men worldwide, presenting a significant global public health challenge that necessitates early detection and personalized treatment. Recently, non-invasive liquid biopsy methods have emerged as promising tools to provide insights into the genetic landscape of PCa and monitor disease progression, aiding decision-making at all stages. Research efforts have concentrated on identifying liquid biopsy biomarkers to improve PCa diagnosis, prognosis, and treatment prediction. This article reviews recent research advances over the last five years utilizing extracellular vesicles (EVs) as a natural biomarker library for PCa, and discusses the clinical translation of EV biomarkers, including ongoing trials and key implementation challenges. The findings underscore the transformative role of liquid biopsy, particularly EV-based biomarkers, in revolutionizing PCa diagnosis, prediction, and treatment.
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Affiliation(s)
- Xiaoxiao Wang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Limin Zhang
- Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, 434000, China; The Third Clinical Medical College of Yangtze University, Jingzhou, 434000, China
| | - Le Cheng
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Yufei Wang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Mengnan Li
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Jiahui Yu
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Zhaowu Ma
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Paul Chi-Lui Ho
- School of Pharmacy, Monash University Malaysia, 47500, Subang Jaya, Malaysia
| | - Gautam Sethi
- NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Xiaoguang Chen
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China.
| | - Lingzhi Wang
- NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
| | - Boon-Cher Goh
- NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, 119228, Singapore
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8
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Chelnokova IA, Nikitina IA, Starodubtseva MN. Mechanical properties of blood exosomes and lipoproteins after the rat whole blood irradiation with X-rays in vitro explored by atomic force microscopy. Micron 2024; 184:103662. [PMID: 38838454 DOI: 10.1016/j.micron.2024.103662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 05/21/2024] [Accepted: 05/21/2024] [Indexed: 06/07/2024]
Abstract
Blood is a two-component system with two levels of hierarchy: the macrosystem of blood formed elements and the dispersed system of blood nanoparticles. Biological nanoparticles are the key participants in communication between the irradiated and non-irradiated cells and inducers of the non-targeted effects of ionizing radiation. The work aimed at studying by atomic force microscopy the structural, mechanical, and electrical properties of exosomes and lipoproteins (LDL/VLDL) isolated from rat blood after its exposure to X-rays in vitro. MATERIALS AND METHODS The whole blood of Wistar rats fed with a high-fat diet was irradiated with X-rays (1 and 100 Gy) in vitro. The structural and mechanical properties (the elastic modulus and nonspecific adhesion force) of exosome and lipoprotein isolates from the blood by ultracentrifugation method were studied using Bruker Bioscope Resolve atomic force microscope in PF QNM mode, their electric properties (the zeta-potential) was measured by electrophoretic mobility. RESULTS Lipoproteins isolated from non-irradiated blood were softer (Me(LQ; UQ): 7.8(4.9;12.1) MPa) compared to blood nanoparticles of its exosome fraction (34.8(22.6;44.9) MPa) containing both exosomes and non-membrane nanoparticles. X-ray blood irradiation with a dose of 1 Gy significantly weakened the elastic properties of lipoproteins. Exposure of the blood to 100 Gy X-rays made lipoproteins stiffer and their nonspecific adhesive properties stronger. The radiation effects on the mechanical parameters of exosomes and non-membrane nanoparticles in exosome fractions differed. The significant radiation-induced change in electric properties of the studied nanoparticles was detected only for lipoproteins in the blood irradiated with 1 Gy X-rays. The low-dose radiation-induced changes in zeta-potential and increase in lipoprotein size with the appearance of a soft thick surface layer indicate the formation of the modified lipoproteins covered with a corona from macromolecules of irradiated blood. CONCLUSION Our data obtained using the nanomechanical mapping mode of AFM are the first evidence of the significant radiation-induced changes in the structural and mechanical properties of the dispersed system of blood nanoparticles after the X-ray irradiation of the blood.
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Affiliation(s)
- Irina A Chelnokova
- Institute of Radiobiology of the National Academy of Sciences of Belarus, Gomel, Belarus.
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Abou-Ghali NE, Giannakakou P. Advances in metastatic prostate cancer circulating tumor cell enrichment technologies and clinical studies. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2024; 392:151-175. [PMID: 40287219 DOI: 10.1016/bs.ircmb.2024.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
Circulating tumor cells (CTCs) have emerged as a pivotal tool that enables molecular interrogation of patient tumor cells and association with clinical outcomes. In prostate cancer specifically, where tumor biopsies from patients with bone metastasis are extremely challenging, CTCs offer a viable and established source of tumor "biopsy". While the prognostic value of CTC enumeration in metastatic prostate cancer is established, there is a compelling need for molecular CTC characterization for effective patient stratification and disease management. The clinical utility of CTCs has been advanced by the evolution of enrichment technologies and their molecular characterization. Enrichment technologies have evolved from strictly EpCAM-based enrichment to antigen-agnostic enrichment, while their clinical utility has evolved from enumeration to advanced downstream analyses including CTC proteomics, transcriptomics and genomics. This chapter offers a comprehensive overview of recent advancements in CTC enrichment and analytical technologies while highlighting pivotal clinical studies in prostate cancer, that utilize CTCs to determine the molecular basis of clinical response and resistance, to assist in disease management and treatment customization.
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Smack C, Johnson B, Nyalwidhe JO, Semmes OJ, Yang L. Small extracellular vesicles: Roles and clinical application in prostate cancer. Adv Cancer Res 2024; 161:119-190. [PMID: 39032949 DOI: 10.1016/bs.acr.2024.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
Prostate cancer is a significant health problem in the United States. It is remarkably heterogenous, ranging from slow growing disease amenable to active surveillance to highly aggressive forms requiring active treatments. Therefore, being able to precisely determine the nature of disease and appropriately match patients to available and/or novel therapeutics is crucial to improve patients' overall outcome and quality of life. Recently small extracellular vesicles (sEVs), a subset of nanoscale membranous vesicles secreted by various cells, have emerged as important analytes for liquid biopsy and promising vehicles for drug delivery. sEVs contain various biomolecules such as genetic material, proteins, and lipids that recapitulate the characteristics and state of their donor cells. The application of existing and newly developed technologies has resulted in an increased depth of knowledge about biophysical structures, biogenesis, and functions of sEVs. In prostate cancer patients, tumor-derived sEVs can be isolated from biofluids, commonly urine and blood. They mediate intercellular signaling within the tumor microenvironment and distal organ-specific sites, supporting cancer initiation, progression, and metastasis. A mounting body of evidence suggests that sEV components can be potent biomarkers for prostate cancer diagnosis, prognosis, and prediction of disease progression and treatment response. Due to enhanced circulation stability and bio-barrier permeability, sEVs can be also used as effective drug delivery carriers to improve the efficacy and specificity of anti-tumor therapies. This review discusses recent studies on sEVs in prostate cancer and is focused on their role as biomarkers and drug delivery vehicles in the clinical management of prostate cancer.
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Affiliation(s)
- Caleb Smack
- Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States
| | - Benjamin Johnson
- Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States
| | - Julius O Nyalwidhe
- Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States
| | - O John Semmes
- Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States
| | - Lifang Yang
- Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States.
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11
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Skoczylas Ł, Gawin M, Fochtman D, Widłak P, Whiteside TL, Pietrowska M. Immune capture and protein profiling of small extracellular vesicles from human plasma. Proteomics 2024; 24:e2300180. [PMID: 37713108 PMCID: PMC11046486 DOI: 10.1002/pmic.202300180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/11/2023] [Accepted: 08/14/2023] [Indexed: 09/16/2023]
Abstract
Extracellular vesicles (EVs), the key players in inter-cellular communication, are produced by all cell types and are present in all body fluids. Analysis of the proteome content is an important approach in structural and functional studies of these vesicles. EVs circulating in human plasma are heterogeneous in size, cellular origin, and functions. This heterogeneity and the potential presence of contamination with plasma components such as lipoprotein particles and soluble plasma proteins represent a challenge in profiling the proteome of EV subsets by mass spectrometry. An immunocapture strategy prior to mass spectrometry may be used to isolate a homogeneous subpopulation of small EVs (sEV) with a specific endocytic origin from plasma or other biofluids. Immunocapture selectively separates EV subpopulations in biofluids based on the presence of a unique protein carried on the vesicle surface. The advantages and disadvantages of EV immune capture as a preparative step for mass spectrometry are discussed.
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Affiliation(s)
- Łukasz Skoczylas
- Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland
| | - Marta Gawin
- Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland
| | - Daniel Fochtman
- Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland
- Silesian University of Technology, 44-100 Gliwice, Poland
| | - Piotr Widłak
- Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Theresa L. Whiteside
- UPMC Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
- Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
| | - Monika Pietrowska
- Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland
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12
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Al-Daffaie FM, Al-Mudhafar SF, Alhomsi A, Tarazi H, Almehdi AM, El-Huneidi W, Abu-Gharbieh E, Bustanji Y, Alqudah MAY, Abuhelwa AY, Guella A, Alzoubi KH, Semreen MH. Metabolomics and Proteomics in Prostate Cancer Research: Overview, Analytical Techniques, Data Analysis, and Recent Clinical Applications. Int J Mol Sci 2024; 25:5071. [PMID: 38791108 PMCID: PMC11120916 DOI: 10.3390/ijms25105071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 04/26/2024] [Accepted: 04/26/2024] [Indexed: 05/26/2024] Open
Abstract
Prostate cancer (PCa) is a significant global contributor to mortality, predominantly affecting males aged 65 and above. The field of omics has recently gained traction due to its capacity to provide profound insights into the biochemical mechanisms underlying conditions like prostate cancer. This involves the identification and quantification of low-molecular-weight metabolites and proteins acting as crucial biochemical signals for early detection, therapy assessment, and target identification. A spectrum of analytical methods is employed to discern and measure these molecules, revealing their altered biological pathways within diseased contexts. Metabolomics and proteomics generate refined data subjected to detailed statistical analysis through sophisticated software, yielding substantive insights. This review aims to underscore the major contributions of multi-omics to PCa research, covering its core principles, its role in tumor biology characterization, biomarker discovery, prognostic studies, various analytical technologies such as mass spectrometry and Nuclear Magnetic Resonance, data processing, and recent clinical applications made possible by an integrative "omics" approach. This approach seeks to address the challenges associated with current PCa treatments. Hence, our research endeavors to demonstrate the valuable applications of these potent tools in investigations, offering significant potential for understanding the complex biochemical environment of prostate cancer and advancing tailored therapeutic approaches for further development.
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Affiliation(s)
- Fatima M. Al-Daffaie
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.M.A.-D.); (S.F.A.-M.); (A.A.); (H.T.); (A.M.A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
| | - Sara F. Al-Mudhafar
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.M.A.-D.); (S.F.A.-M.); (A.A.); (H.T.); (A.M.A.)
| | - Aya Alhomsi
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.M.A.-D.); (S.F.A.-M.); (A.A.); (H.T.); (A.M.A.)
| | - Hamadeh Tarazi
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.M.A.-D.); (S.F.A.-M.); (A.A.); (H.T.); (A.M.A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
| | - Ahmed M. Almehdi
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.M.A.-D.); (S.F.A.-M.); (A.A.); (H.T.); (A.M.A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
| | - Waseem El-Huneidi
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates;
| | - Eman Abu-Gharbieh
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- School of Pharmacy, The University of Jordan, Amman 11942, Jordan
| | - Yasser Bustanji
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates;
- School of Pharmacy, The University of Jordan, Amman 11942, Jordan
| | - Mohammad A. Y. Alqudah
- Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates;
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Ahmad Y. Abuhelwa
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
- Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates;
| | - Adnane Guella
- Nephrology Department, University Hospital Sharjah, Sharjah 27272, United Arab Emirates;
| | - Karem H. Alzoubi
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
- Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates;
| | - Mohammad H. Semreen
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.M.A.-D.); (S.F.A.-M.); (A.A.); (H.T.); (A.M.A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (W.E.-H.); (E.A.-G.); (A.Y.A.); (K.H.A.)
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13
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Liao C, Huang Z, Liu J, Deng M, Wang L, Chen Y, Li J, Zhao J, Luo X, Zhu J, Wu Q, Fu W, Sun B, Zheng J. Role of extracellular vesicles in castration-resistant prostate cancer. Crit Rev Oncol Hematol 2024; 197:104348. [PMID: 38588967 DOI: 10.1016/j.critrevonc.2024.104348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 04/03/2024] [Accepted: 04/04/2024] [Indexed: 04/10/2024] Open
Abstract
Prostate cancer (PCa) is a common health threat to men worldwide, and castration-resistant PCa (CRPC) is the leading cause of PCa-related deaths. Extracellular vesicles (EVs) are lipid bilayer compartments secreted by living cells that are important mediators of intercellular communication. EVs regulate the biological processes of recipient cells by transmitting heterogeneous cargoes, contributing to CRPC occurrence, progression, and drug resistance. These EVs originate not only from malignant cells, but also from various cell types within the tumor microenvironment. EVs are widely dispersed throughout diverse biological fluids and are attractive biomarkers derived from noninvasive liquid biopsy techniques. EV quantities and cargoes have been tested as potential biomarkers for CRPC diagnosis, progression, drug resistance, and prognosis; however, technical barriers to their clinical application continue to exist. Furthermore, exogenous EVs may provide tools for new therapies for CRPC. This review summarizes the current evidence on the role of EVs in CRPC.
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Affiliation(s)
- Chaoyu Liao
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Zeyu Huang
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Jingui Liu
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Min Deng
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Leyi Wang
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Yutong Chen
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Jia Li
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Jiang Zhao
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Xing Luo
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Jingzhen Zhu
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Qingjian Wu
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Weihua Fu
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Bishao Sun
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China.
| | - Ji Zheng
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China.
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14
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Machado CML, Skubal M, Haedicke K, Silva FP, Stater EP, Silva TLADO, Costa ET, Masotti C, Otake AH, Andrade LNS, Junqueira MDS, Hsu HT, Das S, Larney BM, Pratt EC, Romin Y, Fan N, Manova-Todorova K, Pomper M, Grimm J. Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors. J Control Release 2023; 364:312-325. [PMID: 37884210 PMCID: PMC10842212 DOI: 10.1016/j.jconrel.2023.10.038] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 09/19/2023] [Accepted: 10/23/2023] [Indexed: 10/28/2023]
Abstract
Cell membrane-derived particles (Mp) are rounded membrane-enclosed particles that are shed from tumor cells. Mp are formed from tumor membranes and are capable of tumor targeting and immunotherapeutic agents because they share membrane homology with parental cells; thus, they are under consideration as a drug delivery vehicle. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein with enzymatic functionality, is highly expressed in Mp and extracellular vesicles (EV) from prostate cancer (PCa) with poor clinical prognosis. Although PSMA expression was previously shown in EV and Mp isolated from cell lines and from the blood of patients with high-grade PCa, no pathophysiological effects have been linked to PCa-derived Mp. Here, we compared Mp from PSMA-expressing (PSMA-Mp) and PSMA-non-expressing (WT-Mp) cells side by side in vitro and in vivo. PSMA-Mp can transfer PSMA and new phenotypic characteristics to the tumor microenvironment. The consequence of PSMA transfer to cells and increased secretion of vascular endothelial growth factor-A (VEGF-A), pro-angiogenic and pro-lymphangiogenic mediators, with increased 4E binding protein 1 (4EBP-1) phosphorylation.
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Affiliation(s)
- Camila M L Machado
- Laboratorio de Investigação Médica de Medicina Nuclear-LIM-43, Departamento de Radiologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403911, Brazil; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Magdalena Skubal
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Katja Haedicke
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Fabio P Silva
- Laboratory of Molecular Pathology of Cancer, Faculty of Health Sciences and Medicine, University of Brasilia, Brasília 70910900, Brazil; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Evan P Stater
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Thais L A de O Silva
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Breast Cancer Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Erico T Costa
- Centro de Oncologia Molecular, Hospital Sírio Libanês, São Paulo, SP 01308050, Brazil
| | - Cibele Masotti
- Centro de Oncologia Molecular, Hospital Sírio Libanês, São Paulo, SP 01308050, Brazil
| | - Andreia H Otake
- Centro de Investigação Translacional em Oncologia - Instituto do Câncer do Estado de São Paulo - Faculdade de Medicina da Universidade de São Paulo, Departamento de Radiologia e Oncologia, São Paulo, SP 01246000, Brazil
| | - Luciana N S Andrade
- Centro de Investigação Translacional em Oncologia - Instituto do Câncer do Estado de São Paulo - Faculdade de Medicina da Universidade de São Paulo, Departamento de Radiologia e Oncologia, São Paulo, SP 01246000, Brazil
| | - Mara de S Junqueira
- Centro de Investigação Translacional em Oncologia - Instituto do Câncer do Estado de São Paulo - Faculdade de Medicina da Universidade de São Paulo, Departamento de Radiologia e Oncologia, São Paulo, SP 01246000, Brazil
| | - Hsiao-Ting Hsu
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Sudeep Das
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Benedict Mc Larney
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Edwin C Pratt
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Yevgeniy Romin
- Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Ning Fan
- Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Katia Manova-Todorova
- Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Martin Pomper
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Jan Grimm
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
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15
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Lv T, Li Z, Wang D, Guo X, Zhang X, Cao J, Wang Z. Role of exosomes in prostate cancer bone metastasis. Arch Biochem Biophys 2023; 748:109784. [PMID: 37816420 DOI: 10.1016/j.abb.2023.109784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 10/05/2023] [Accepted: 10/07/2023] [Indexed: 10/12/2023]
Abstract
Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.
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Affiliation(s)
- Tingting Lv
- Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, PR China
| | - Zijie Li
- Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, PR China
| | - Dehua Wang
- Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, PR China
| | - Xiaojin Guo
- Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, PR China
| | - Xiaokuan Zhang
- Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, PR China
| | - Jing Cao
- Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, PR China
| | - Zhiyu Wang
- Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, PR China.
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16
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Chen TY, Mihalopoulos M, Zuluaga L, Rich J, Ganta T, Mehrazin R, Tsao CK, Tewari A, Gonzalez-Kozlova E, Badani K, Dogra N, Kyprianou N. Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer. Int J Mol Sci 2023; 24:14713. [PMID: 37834162 PMCID: PMC10573190 DOI: 10.3390/ijms241914713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 09/02/2023] [Accepted: 09/03/2023] [Indexed: 10/15/2023] Open
Abstract
Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.
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Affiliation(s)
- Tzu-Yi Chen
- Department of Pathology & Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (T.-Y.C.); (A.T.)
| | - Meredith Mihalopoulos
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (M.M.); (L.Z.); (J.R.); (R.M.); (K.B.)
| | - Laura Zuluaga
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (M.M.); (L.Z.); (J.R.); (R.M.); (K.B.)
| | - Jordan Rich
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (M.M.); (L.Z.); (J.R.); (R.M.); (K.B.)
| | - Teja Ganta
- Department of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (T.G.); (C.-K.T.)
| | - Reza Mehrazin
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (M.M.); (L.Z.); (J.R.); (R.M.); (K.B.)
| | - Che-Kai Tsao
- Department of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (T.G.); (C.-K.T.)
| | - Ash Tewari
- Department of Pathology & Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (T.-Y.C.); (A.T.)
| | - Edgar Gonzalez-Kozlova
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Ketan Badani
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (M.M.); (L.Z.); (J.R.); (R.M.); (K.B.)
| | - Navneet Dogra
- Department of Pathology & Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (T.-Y.C.); (A.T.)
| | - Natasha Kyprianou
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (M.M.); (L.Z.); (J.R.); (R.M.); (K.B.)
- The Tisch Cancer Institute, Mount Sinai Health, New York, NY 10029, USA
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17
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Zhang J, Wu J, Wang G, He L, Zheng Z, Wu M, Zhang Y. Extracellular Vesicles: Techniques and Biomedical Applications Related to Single Vesicle Analysis. ACS NANO 2023; 17:17668-17698. [PMID: 37695614 DOI: 10.1021/acsnano.3c03172] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Extracellular vesicles (EVs) are extensively dispersed lipid bilayer membrane vesicles involved in the delivery and transportation of molecular payloads to certain cell types to facilitate intercellular interactions. Their significant roles in physiological and pathological processes make EVs outstanding biomarkers for disease diagnosis and treatment monitoring as well as ideal candidates for drug delivery. Nevertheless, differences in the biogenesis processes among EV subpopulations have led to a diversity of biophysical characteristics and molecular cargos. Additionally, the prevalent heterogeneity of EVs has been found to substantially hamper the sensitivity and accuracy of disease diagnosis and therapeutic monitoring, thus impeding the advancement of clinical applications. In recent years, the evolution of single EV (SEV) analysis has enabled an in-depth comprehension of the physical properties, molecular composition, and biological roles of EVs at the individual vesicle level. This review examines the sample acquisition tactics prior to SEV analysis, i.e., EV isolation techniques, and outlines the current state-of-the-art label-free and label-based technologies for SEV identification. Furthermore, the challenges and prospects of biomedical applications based on SEV analysis are systematically discussed.
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Affiliation(s)
- Jie Zhang
- Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
| | - Jiacheng Wu
- Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
| | - Guanzhao Wang
- Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
| | - Luxuan He
- Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
| | - Ziwei Zheng
- Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
| | - Minhao Wu
- Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Yuanqing Zhang
- Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
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18
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Nair S, Ormazabal V, Carrion F, Handberg A, McIntyre H, Salomon C. Extracellular vesicle-mediated targeting strategies for long-term health benefits in gestational diabetes. Clin Sci (Lond) 2023; 137:1311-1332. [PMID: 37650554 PMCID: PMC10472199 DOI: 10.1042/cs20220150] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 07/23/2023] [Accepted: 08/09/2023] [Indexed: 09/01/2023]
Abstract
Extracellular vesicles (EVs) are critical mediators of cell communication, playing important roles in regulating molecular cross-talk between different metabolic tissues and influencing insulin sensitivity in both healthy and gestational diabetes mellitus (GDM) pregnancies. The ability of EVs to transfer molecular cargo between cells imbues them with potential as therapeutic agents. During pregnancy, the placenta assumes a vital role in metabolic regulation, with multiple mechanisms of placenta-mediated EV cross-talk serving as central components in GDM pathophysiology. This review focuses on the role of the placenta in the pathophysiology of GDM and explores the possibilities and prospects of targeting the placenta to address insulin resistance and placental dysfunction in GDM. Additionally, we propose the use of EVs as a novel method for targeted therapeutics in treating the dysfunctional placenta. The primary aim of this review is to comprehend the current status of EV targeting approaches and assess the potential application of these strategies in placental therapeutics, thereby delivering molecular cargo and improving maternal and fetal outcomes in GDM. We propose that EVs have the potential to revolutionize GDM management, offering hope for enhanced maternal-fetal health outcomes and more effective treatments.
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Affiliation(s)
- Soumyalekshmi Nair
- Translational Extracellular Vesicle in Obstetrics and Gynae-Oncology Group, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Australia
| | - Valeska Ormazabal
- Department of Pharmacology, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile
| | - Flavio Carrion
- Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile
| | - Aase Handberg
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
| | - H David McIntyre
- Mater Research, Faculty of Medicine, University of Queensland, Mater Health, South Brisbane, Australia
| | - Carlos Salomon
- Translational Extracellular Vesicle in Obstetrics and Gynae-Oncology Group, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Australia
- Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile
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19
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Choi WWY, Sánchez C, Li JJ, Dinarvand M, Adomat H, Ghaffari M, Khoja L, Vafaee F, Joshua AM, Chi KN, Guns EST, Hosseini-Beheshti E. Extracellular vesicles from biological fluids as potential markers in castration resistant prostate cancer. J Cancer Res Clin Oncol 2023; 149:4701-4717. [PMID: 36222898 PMCID: PMC10349738 DOI: 10.1007/s00432-022-04391-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/03/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal cells, and have great potential to be used as markers for disease initiation, progression, and response to treatment. This under-utilised tool provides insights into a better understanding of prostate cancer. METHODS EV from serum and urine of healthy men and castration-resistant prostate cancer (CRPC) patients were isolated and characterised by transmission electron microscopy, particle size analysis, and western blot. Proteomic and cholesterol liquid chromatography-mass spectrometry (LC-MS) analyses were conducted. RESULTS There was a successful enrichment of small EV/exosomes isolated from serum and urine. EV derived from biological fluids of CRPC patients had significant differences in composition when compared with those from healthy controls. Analysis of matched serum and urine samples from six prostate cancer patients revealed specific EV proteins common in both types of biological fluid for each patient. CONCLUSION Some of the EV proteins identified from our analyses have potential to be used as CRPC markers. These markers may depict a pattern in cancer progression through non-invasive sample collection.
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Affiliation(s)
- Wendy W Y Choi
- Vancouver Prostate Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada
| | | | - Jiao Jiao Li
- Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, NSW, 2065, Australia
- School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Mojdeh Dinarvand
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, 2052, Australia
| | - Hans Adomat
- Vancouver Prostate Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada
| | - Mazyar Ghaffari
- Vancouver Prostate Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada
- Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia
| | - Leila Khoja
- St Vincent's Hospital Sydney, Darlinghurst, NSW, 2010, Australia
| | - Fatemeh Vafaee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, 2052, Australia
- UNSW Data Science Hub, University of New South Wales, Kensington, NSW, 2052, Australia
| | - Anthony M Joshua
- St Vincent's Hospital Sydney, Darlinghurst, NSW, 2010, Australia
| | - Kim N Chi
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6, Canada
| | - Emma S Tomlinson Guns
- Vancouver Prostate Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6, Canada
| | - Elham Hosseini-Beheshti
- Vancouver Prostate Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada.
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.
- The Sydney Nano Institute, The University of Sydney, Sydney, NSW, 2006, Australia.
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20
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Wang JJ, Sun N, Lee YT, Kim M, Vagner T, Rohena-Rivera K, Wang Z, Chen Z, Zhang RY, Lee J, Zhang C, Tang H, Widjaja J, Zhang TX, Qi D, Teng PC, Jan YJ, Hou KC, Hamann C, Sandler HM, Daskivich TJ, Luthringer DJ, Bhowmick NA, Pei R, You S, Di Vizio D, Tseng HR, Chen JF, Zhu Y, Posadas EM. Prostate cancer extracellular vesicle digital scoring assay - a rapid noninvasive approach for quantification of disease-relevant mRNAs. NANO TODAY 2023; 48:101746. [PMID: 36711067 PMCID: PMC9879227 DOI: 10.1016/j.nantod.2022.101746] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Optimizing outcomes in prostate cancer (PCa) requires precision in characterization of disease status. This effort was directed at developing a PCa extracellular vesicle (EV) Digital Scoring Assay (DSA) for detecting metastasis and monitoring progression of PCa. PCa EV DSA is comprised of an EV purification device (i.e., EV Click Chip) and reverse-transcription droplet digital PCR that quantifies 11 PCa-relevant mRNA in purified PCa-derived EVs. A Met score was computed for each plasma sample based on the expression of the 11-gene panel using the weighted Z score method. Under optimized conditions, the EV Click Chips outperformed the ultracentrifugation or precipitation method of purifying PCa-derived EVs from artificial plasma samples. Using PCa EV DSA, the Met score distinguished metastatic (n = 20) from localized PCa (n = 20) with an area under the receiver operating characteristic curve of 0.88 (95% CI:0.78-0.98). Furthermore, longitudinal analysis of three PCa patients showed the dynamics of the Met scores reflected clinical behavior even when disease was undetectable by imaging. Overall, a sensitive PCa EV DSA was developed to identify metastatic PCa and reveal dynamic disease states noninvasively. This assay may complement current imaging tools and blood-based tests for timely detection of metastatic progression that can improve care for PCa patients.
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Affiliation(s)
- Jasmine J. Wang
- Division of Medical Oncology, Department of Medicine,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Na Sun
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
- Key Laboratory for Nano-Bio Interface, Suzhou Institute of
Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese
Academy of Sciences, Suzhou, PR China
| | - Yi-Te Lee
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Minhyung Kim
- Department of Biomedical Sciences, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
| | - Tatyana Vagner
- Department of Surgery, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
| | | | - Zhili Wang
- Key Laboratory for Nano-Bio Interface, Suzhou Institute of
Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese
Academy of Sciences, Suzhou, PR China
| | - Zijing Chen
- Division of Medical Oncology, Department of Medicine,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Ryan Y. Zhang
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Junseok Lee
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Ceng Zhang
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Hubert Tang
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Josephine Widjaja
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Tiffany X. Zhang
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Dongping Qi
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Pai-Chi Teng
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
| | - Yu Jen Jan
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
| | - Kuan-Chu Hou
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
| | - Candace Hamann
- Division of Medical Oncology, Department of Medicine,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Howard M. Sandler
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- Department of Radiation Oncology, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
| | - Timothy J. Daskivich
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- Division of Urology, Department of Surgery, Cedars-Sinai
Medical Center, Los Angeles, CA, USA
| | - Daniel J. Luthringer
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- Department of Pathology and Laboratory Medicine,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Neil A. Bhowmick
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
- Department of Medicine, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
| | - Renjun Pei
- Key Laboratory for Nano-Bio Interface, Suzhou Institute of
Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese
Academy of Sciences, Suzhou, PR China
| | - Sungyong You
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
- Department of Surgery, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
| | - Dolores Di Vizio
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
- Department of Surgery, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
- Department of Pathology and Laboratory Medicine,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Hsian-Rong Tseng
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
- Jonsson Comprehensive Cancer Center, David Geffen School
of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Jie-Fu Chen
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | - Yazhen Zhu
- California NanoSystems Institute, Crump Institute for
Molecular Imaging, Department of Molecular and Medical Pharmacology, University of
California, Los Angeles, Los Angeles, CA, USA
- Jonsson Comprehensive Cancer Center, David Geffen School
of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Edwin M. Posadas
- Division of Medical Oncology, Department of Medicine,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
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21
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Robinson H, Roberts MJ, Gardiner RA, Hill MM. Extracellular vesicles for precision medicine in prostate cancer - Is it ready for clinical translation? Semin Cancer Biol 2023; 89:18-29. [PMID: 36681206 DOI: 10.1016/j.semcancer.2023.01.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 01/10/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023]
Abstract
Biofluid-based biomarker tests hold great promise for precision medicine in prostate cancer (PCa) clinical practice. Extracellular vesicles (EV) are established as intercellular messengers in cancer development with EV cargos, including protein and nucleic acids, having the potential to serve as biofluid-based biomarkers. Recent clinical studies have begun to evaluate EV-based biomarkers for PCa diagnosis, prognosis, and disease/therapy resistance monitoring. Promising results have led to PCa EV biomarker validation studies which are currently underway with the next challenge being translation to robust clinical assays. However, EV research studies generally use low throughput EV isolation methods and costly molecular profiling technologies that are not suitable for clinical assays. Here, we consider the technical hurdles in translating EV biomarker research findings into precise and cost-effective clinical biomarker assays. Novel microfluidic devices coupling EV extraction with sensitive antibody-based biomarker detection are already being explored for point-of-care applications for rapid provision in personalised medicine approaches.
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Affiliation(s)
- Harley Robinson
- QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland, Australia.
| | - Matthew J Roberts
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Brisbane, Queensland, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Robert A Gardiner
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Brisbane, Queensland, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Michelle M Hill
- QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland, Australia; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Brisbane, Queensland, Australia.
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22
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K S, T D, M P. Small extracellular vesicles as a multicomponent biomarker platform in urinary tract carcinomas. Front Mol Biosci 2022; 9:916666. [PMID: 36237572 PMCID: PMC9551577 DOI: 10.3389/fmolb.2022.916666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/01/2022] [Indexed: 11/23/2022] Open
Abstract
Extracellular vesicles are a large group of nano-sized vesicles released by all cells. The variety of possible cargo (mRNAs, miRNAs, lncRNAs, proteins, and lipids) and the presence of surface proteins, signaling molecules, and receptor ligands make them a rich source of biomarkers for malignancy diagnosis. One of the groups gathering the most interest in cancer diagnostic applications is small extracellular vesicles (sEVs), with ≤200 nm diameter, mainly composed of exosomes. Many studies were conducted recently, evaluating the diagnostic potential of sEVs in urinary tract carcinomas (UTCs), discovering and clinically evaluating various classes of biomarkers. The amount of research concerning different types of UTCs understandably reflects their incidence. sEV cargos getting the most interest are non-coding RNAs (miRNA and lncRNA). However, implementation of other approaches such as metabolomic and proteomic analysis is also evaluated. The results of many studies indicate that sEVs have an essential role in the cancer process and possess many possible diagnostic and prognostic applications for UTC. The relative ease of obtaining biofluids rich in sEVs (urine and blood) confirms that sEVs are essential for UTC detection in the liquid biopsy approach. A noticeable rise in research quality is observed as more researchers are aware of the research standardization necessity, which is essential for considering the clinical application of their findings.
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23
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Cui X, Fu Q, Wang X, Xia P, Cui X, Bai X, Lu Z. Molecular mechanisms and clinical applications of exosomes in prostate cancer. Biomark Res 2022; 10:56. [PMID: 35906674 PMCID: PMC9338661 DOI: 10.1186/s40364-022-00398-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 07/11/2022] [Indexed: 11/30/2022] Open
Abstract
Prostate cancer (PC) is a common tumor in men, and the incidence rate is high worldwide. Exosomes are nanosized vesicles released by all types of cells into multiple biological fluid types. These vesicles contribute to intercellular communication by delivering both nucleic acids and proteins to recipient cells. In recent years, many studies have explored the mechanisms by which exosomes mediate the epithelial-mesenchymal transition, angiogenesis, tumor microenvironment establishment, and drug resistance acquisition in PC, and the mechanisms that have been identified and the molecules involved have provided new perspectives for the possible discovery of novel diagnostic markers in PC. Furthermore, the excellent biophysical properties of exosomes, such as their high stability, high biocompatibility and ability to cross biological barriers, have made exosomes promising candidates for use in novel targeted drug delivery system development. In this review, we summarize the roles of exosomes in the growth and signal transmission in PC and show the promising future of exosome contributions to PC diagnostics and treatment.
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Affiliation(s)
- Xiaolin Cui
- Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.,Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China
| | - Qiang Fu
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xueying Wang
- Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.,Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China
| | - Pengcheng Xia
- Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.,Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China
| | - Xianglun Cui
- Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.,Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China
| | - Xiaohui Bai
- Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.,Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China
| | - Zhiming Lu
- Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. .,Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China.
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24
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Zhang X, Takeuchi T, Takeda A, Mochizuki H, Nagai Y. Comparison of serum and plasma as a source of blood extracellular vesicles: Increased levels of platelet-derived particles in serum extracellular vesicle fractions alter content profiles from plasma extracellular vesicle fractions. PLoS One 2022; 17:e0270634. [PMID: 35749554 PMCID: PMC9231772 DOI: 10.1371/journal.pone.0270634] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 06/15/2022] [Indexed: 11/30/2022] Open
Abstract
Extracellular vesicles (EVs) have attracted much attention as potential diagnostic biomarkers for human diseases. Although both plasma and serum are utilized as a source of blood EVs, it remains unclear whether, how and to what extent the choice of plasma and serum affects the experimental results. To address this issue, in this study, we performed comprehensive characterization of EV fractions derived from plasma and serum, and investigated the differences between these blood EVs. We demonstrated by nanoparticle tracking analysis that EV fractions derived from serum contain more particles than those from plasma of mice. Proteomic analysis demonstrated that platelet-associated proteins are selectively enriched in serum EV fractions from both mice and humans. A literature review of proteomic data of human blood EVs reported by other groups further confirmed that selective enrichment of platelet-associated proteins is commonly observed in serum EVs, and confers different proteome profiles to plasma EVs. Our data provide experimental evidence that EV fractions derived from serum generally contain additional EVs that are released from platelets, which may qualitatively and quantitatively alter EV profiles when using serum as a source of blood EVs.
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Affiliation(s)
- Xiaoman Zhang
- Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Toshihide Takeuchi
- Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Life Science Research Institute, Kindai University, Osaka-Sayama, Osaka, Japan
- PRESTO, Japan Science and Technology Agency (JST), Osaka, Japan
- * E-mail: (TT); (YN)
| | - Akiko Takeda
- Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Hideki Mochizuki
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Yoshitaka Nagai
- Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- * E-mail: (TT); (YN)
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25
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Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges. Br J Cancer 2022; 127:1394-1402. [PMID: 35715640 PMCID: PMC9553885 DOI: 10.1038/s41416-022-01881-9] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 05/19/2022] [Accepted: 06/01/2022] [Indexed: 12/19/2022] Open
Abstract
Liquid biopsy has been established as a powerful, minimally invasive, tool to detect clinically actionable aberrations across numerous cancer types in real-time. With the development of new therapeutic agents in prostate cancer (PC) including DNA repair targeted therapies, this is especially attractive. However, there is unclarity on how best to screen for PC, improve risk stratification and ultimately how to treat advanced disease. Therefore, there is an urgent need to develop better biomarkers to help guide oncologists' decisions in these settings. Circulating tumour cells (CTCs), exosomes and cell-free DNA/RNA (cfDNA/cfRNA) analysis, including epigenetic features such as methylation, have all shown potential in prognostication, treatment response assessment and detection of emerging mechanisms of resistance. However, there are still challenges to overcome prior to implementing liquid biopsies in routine clinical practice such as preanalytical considerations including blood collection and storage, the cost of CTC isolation and enrichment, low-circulating tumour content as a limitation for genomic analysis and how to better interpret the sequencing data generated. In this review, we describe an overview of the up-to-date clinical opportunities in the management of PC through blood-based liquid biopsies and the next steps for its implementation in personalised treatment guidance.
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26
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Dathathri E, Isebia KT, Abali F, Lolkema MP, Martens JWM, Terstappen LWMM, Bansal R. Liquid Biopsy Based Circulating Biomarkers in Metastatic Prostate Cancer. Front Oncol 2022; 12:863472. [PMID: 35669415 PMCID: PMC9165750 DOI: 10.3389/fonc.2022.863472] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 04/22/2022] [Indexed: 12/14/2022] Open
Abstract
Prostate cancer is the most dominant male malignancy worldwide. The clinical presentation of prostate cancer ranges from localized indolent to rapidly progressing lethal metastatic disease. Despite a decline in death rate over the past years, with the advent of early diagnosis and new treatment options, challenges remain towards the management of metastatic prostate cancer, particularly metastatic castration sensitive prostate cancer (mCSPC) and castration resistant prostate cancer (mCRPC). Current treatments involve a combination of chemotherapy with androgen deprivation therapy and/or androgen receptor signalling inhibitors. However, treatment outcomes are heterogeneous due to significant tumor heterogeneity indicating a need for better prognostic biomarkers to identify patients with poor outcomes. Liquid biopsy has opened a plethora of opportunities from early diagnosis to (personalized) therapeutic disease interventions. In this review, we first provide recent insights about (metastatic) prostate cancer and its current treatment landscape. We highlight recent studies involving various circulating biomarkers such as circulating tumor cells, genetic markers, circulating nucleic acids, extracellular vesicles, tumor-educated platelets, and the secretome from (circulating) tumor cells and tumor microenvironment in metastatic prostate cancer. The comprehensive array of biomarkers can provide a powerful approach to understanding the spectrum of prostate cancer disease and guide in developing improved and personalized treatments for patients.
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Affiliation(s)
- Eshwari Dathathri
- Department of Medical Cell BioPhysics, Faculty of Science and Technology, Technical Medical Center, University of Twente, Enschede, Netherlands
| | - Khrystany T. Isebia
- Erasmus Medical Center Cancer Institute, University Medical Center Rotterdam, Department of Medical Oncology, Rotterdam, Netherlands
| | - Fikri Abali
- Department of Medical Cell BioPhysics, Faculty of Science and Technology, Technical Medical Center, University of Twente, Enschede, Netherlands
| | - Martijn P. Lolkema
- Erasmus Medical Center Cancer Institute, University Medical Center Rotterdam, Department of Medical Oncology, Rotterdam, Netherlands
| | - John W. M. Martens
- Erasmus Medical Center Cancer Institute, University Medical Center Rotterdam, Department of Medical Oncology, Rotterdam, Netherlands
| | - Leon W. M. M. Terstappen
- Department of Medical Cell BioPhysics, Faculty of Science and Technology, Technical Medical Center, University of Twente, Enschede, Netherlands
| | - Ruchi Bansal
- Department of Medical Cell BioPhysics, Faculty of Science and Technology, Technical Medical Center, University of Twente, Enschede, Netherlands
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27
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Younas N, Fernandez Flores LC, Hopfner F, Höglinger GU, Zerr I. A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin. Transl Neurodegener 2022; 11:28. [PMID: 35527262 PMCID: PMC9082915 DOI: 10.1186/s40035-022-00301-5] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood–brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.
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Khan T, Becker TM, Scott KF, Descallar J, de Souza P, Chua W, Ma Y. Prognostic and Predictive Value of Liquid Biopsy-Derived Androgen Receptor Variant 7 (AR-V7) in Prostate Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:868031. [PMID: 35372002 PMCID: PMC8971301 DOI: 10.3389/fonc.2022.868031] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 02/21/2022] [Indexed: 12/21/2022] Open
Abstract
In advanced prostate cancer, access to recent diagnostic tissue samples is restricted and this affects the analysis of the association of evolving biomarkers such as AR-V7 with metastatic castrate resistance. Liquid biopsies are emerging as alternative analytes. To clarify clinical value of AR-V7 detection from liquid biopsies, here we performed a meta-analysis on the prognostic and predictive value of androgen receptor variant 7 (AR-V7) detected from liquid biopsy for patients with prostate cancer (PC), three databases, the Embase, Medline, and Scopus were searched up to September 2021. A total of 37 studies were included. The effects of liquid biopsy AR-V7 status on overall survival (OS), radiographic progression-free survival (PFS), and prostate-specific antigen (PSA)-PFS were calculated with RevMan 5.3 software. AR-V7 positivity detected in liquid biopsy significantly associates with worse OS, PFS, and PSA-PFS (P <0.00001). A subgroup analysis of patients treated with androgen receptor signaling inhibitors (ARSi such as abiraterone and enzalutamide) showed a significant association of AR-V7 positivity with poorer OS, PFS, and PSA-PFS. A statistically significant association with OS was also found in taxane-treated patients (P = 0.04), but not for PFS (P = 0.21) or PSA-PFS (P = 0.93). For AR-V7 positive patients, taxane treatment has better OS outcomes than ARSi (P = 0.01). Study quality, publication bias and sensitivity analysis were integrated in the assessment. Our data show that liquid biopsy AR-V7 is a clinically useful biomarker that is associated with poor outcomes of ARSi-treated castrate resistant PC (CRPC) patients and thus has the potential to guide patient management and also to stratify patients for clinical trials. More studies on chemotherapy-treated patients are warranted.
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Affiliation(s)
- Tanzila Khan
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Medical Oncology, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
- Centre of Circulating Tumour Cell Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
| | - Therese M. Becker
- Medical Oncology, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
- Centre of Circulating Tumour Cell Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
- South West Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW, Australia
| | - Kieran F. Scott
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Medical Oncology, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
| | - Joseph Descallar
- South West Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW, Australia
- Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
| | - Paul de Souza
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Medical Oncology, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
- School of Medicine, University of New South Wales, Kensington, NSW, Australia
| | - Wei Chua
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Medical Oncology, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
- South West Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW, Australia
- Medical Oncology, Liverpool Hospital, Liverpool, NSW, Australia
| | - Yafeng Ma
- Medical Oncology, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
- Centre of Circulating Tumour Cell Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
- South West Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW, Australia
- *Correspondence: Yafeng Ma,
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Li X, Zhao W, Peng L, Li Y, Nie S, Yu H, Qin Y, Zhang H. Elevated serum extracellular vesicle arginase 1 in type 2 diabetes mellitus: a cross-sectional study in middle-aged and elderly population. BMC Endocr Disord 2022; 22:62. [PMID: 35277141 PMCID: PMC8917686 DOI: 10.1186/s12902-022-00982-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 03/01/2022] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Serum extracellular vesicle (EV)-derived arginase 1 (ARG 1) plays a critical role in diabetes-associated endothelial dysfunction. This study was performed to determine the levels of serum EV-derived ARG 1 in T2DM and non-T2DM participants and to examine the association of serum EV-derived ARG 1 with T2DM incidence. METHODS We performed a cross-sectional study in 103 Chinese, including 73 T2DM patients and 30 non-T2DM. Serum EVs were prepared via ultracentrifugation. Serum EV-derived ARG 1 levels were measured by enzyme-linked immunosorbent assay. The correlations between serum EV-derived ARG 1 and clinical variables were analyzed. The association of serum EV-derived ARG 1 levels with T2DM was determined by multivariate logistic regression analysis. Interaction subgroup analysis was used to evaluate the interaction of the relevant baselines on the association between serum EV-derived ARG 1 levels and T2DM. RESULTS Serum EV-derived ARG 1 levels were significantly higher in T2DM patients compared with non-T2DM patients (p < 0.001). Correlation analysis revealed that serum EV-derived ARG 1 levels were positively associated with fasting plasma glucose (FPG) (r = 0.316, p = 0.001) and glycated hemoglobin (HbA1c) (r = 0.322, p = 0.001). Serum EV-derived ARG 1 levels were significantly associated with T2DM, especially in the subgroup of T2DM for more than 10 years (OR 1.651, 95% CI = 1.066-2.557; P value, 0.025), after adjusting for confounding factors. CONCLUSIONS Elevated concentration of serum EV-derived ARG 1 is closely associated with T2DM.
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Affiliation(s)
- Xinwei Li
- Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Beijing, 100029, China
| | - Wen Zhao
- Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Beijing, 100029, China
| | - Lu Peng
- Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Beijing, 100029, China
| | - Yu Li
- Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Beijing, 100029, China
| | - Shaoping Nie
- Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Huahui Yu
- Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Beijing, 100029, China
| | - Yanwen Qin
- Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Beijing, 100029, China
| | - Huina Zhang
- Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Beijing, 100029, China.
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30
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Grimaldi AM, Salvatore M, Cavaliere C. Diagnostic and prognostic significance of extracellular vesicles in prostate cancer drug resistance: A systematic review of the literature. Prostate Cancer Prostatic Dis 2022:10.1038/s41391-022-00521-w. [PMID: 35264776 DOI: 10.1038/s41391-022-00521-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 02/04/2022] [Accepted: 02/16/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND The clinical behavior of prostate cancer is highly heterogeneous, with most patients diagnosed with localized disease that successfully responds to surgery or radiotherapy. However, a fraction of men relapse after initial treatment because they develop drug resistance. The failure of anticancer drugs leaves resistant cancer cells to survive and proliferate, negatively affecting patient survival. Thus, drug resistance remains a significant obstacle to the effective treatment of prostate cancer patients. In this scenario, the involvement of extracellular vesicles (EVs) in intrinsic and acquired resistance have been reported in several tumors, and accumulating data suggests that their differential content can be used as diagnostic or prognostic factors. Thus, we propose a systematic study of literature to provide a snapshot of the current scenario regarding EVs as diagnostic and prognostic biomarkers resource in resistant prostate cancer. METHODS We performed the current systematic review according to PRISMA guidelines and comprehensively explored PubMed, EMBASE and Google Scholar databases to achieve the article search. RESULTS Thirty-three studies were included and investigated. Among all systematically reviewed EV biomarkers, we found mainly molecules with prognostic significance (61%), molecules with diagnostic relevance (18%), and molecules that serve both purposes (21%). Moreover, among all analyzed molecules isolated from EVs, proteins, mRNAs, and miRNAs emerged to be the most investigated and proposed as potential tools to diagnose or predict resistance/sensitivity to advanced PCa treatments. DISCUSSION Our analysis provides a snapshot of the current scenario regarding EVs as potential clinical biomarkers in resistant PCa. Nevertheless, despite many efforts, the use of EV biomarkers in PCa is currently at an early stage: none of the selected EV biomarkers goes beyond preclinical studies, and their translatability is yet far from clinical settings.
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31
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Wang T, Xing Y, Cheng Z, Yu F. Analysis of Single Extracellular Vesicles for Biomedical Applications with Especial Emphasis on Cancer Investigations. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116604] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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32
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Franzese C, Perrino M, Marzo MA, Badalamenti M, Baldaccini D, D'Agostino G, Marini B, De Vincenzo F, Zucali PA, Scorsetti M. Oligoprogressive castration-resistant prostate cancer treated with metastases-directed stereotactic body radiation therapy: predictive factors for patients' selection. Clin Exp Metastasis 2022; 39:449-457. [PMID: 35190933 DOI: 10.1007/s10585-022-10158-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/13/2022] [Indexed: 12/25/2022]
Abstract
Oligoprogression is defined as limited metastatic clone resistant to on-going systemic treatment that grows in a background of stable or responding systemic disease. Aim of the present study was to analyze oligoprogressive prostate cancer (PC) patients treated with stereotactic body radiation therapy (SBRT) during systemic treatment to identify predictive factors and improve patients' selection. We included PC patients treated with SBRT on a maximum of 3 sites of oligoprogression during systemic therapy. Endpoints were freedom from polymetastatic progression (FPP), local control (LC), distant progression free survival (DPFS), overall survival (OS), and next systemic therapy free survival (NEST-FS). Fifty-three patients were treated on 85 oligoprogressive metastases. Lymph nodes were the most common sites (56.47%), followed by bone (39.29%). Median follow-up was 24.9 months. Rates of FPP at 1- and 2-year were 80.1% and 68.9%, respectively. Median time to polymetastatic progression was 33.7 months. Disease free interval (p = 0.004), site of metastases (p = 0.011), and type of systemic therapy (p = 0.003) were significant for FPP. Switch or intensification of systemic therapy after SBRT was observed in 29 (54.72%) patients with a median NEST-FS of 15.2 months. LC at 1- and 2-year was 94.0% and 92.0%, with PSA doubling time resulted to be significantly associated (p = 0.047). Median DPFS was 8.93 months and median OS was 50.6 months. In conclusion, we confirmed the efficacy of SBRT for oligoprogression from PC, with the potential to prolong the on-going systemic therapy and interrupt the metastatic cascade.
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Affiliation(s)
- Ciro Franzese
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy. .,Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy. .,Humanitas Research Hospital IRCCS, Humanitas University, Via Manzoni 56, Rozzano, Milan, Italy.
| | - Matteo Perrino
- Department of Oncology, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Marco Antonio Marzo
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy.,Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Marco Badalamenti
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Davide Baldaccini
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Giuseppe D'Agostino
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Beatrice Marini
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy.,Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Fabio De Vincenzo
- Department of Oncology, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Paolo Andrea Zucali
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy.,Department of Oncology, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy.,Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
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33
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Ramirez-Garrastacho M, Bajo-Santos C, Line A, Martens-Uzunova ES, de la Fuente JM, Moros M, Soekmadji C, Tasken KA, Llorente A. Extracellular vesicles as a source of prostate cancer biomarkers in liquid biopsies: a decade of research. Br J Cancer 2022; 126:331-350. [PMID: 34811504 PMCID: PMC8810769 DOI: 10.1038/s41416-021-01610-8] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 01/02/2023] Open
Abstract
Prostate cancer is a global cancer burden and considerable effort has been made through the years to identify biomarkers for the disease. Approximately a decade ago, the potential of analysing extracellular vesicles in liquid biopsies started to be envisaged. This was the beginning of a new exciting area of research investigating the rich molecular treasure found in extracellular vesicles to identify biomarkers for a variety of diseases. Vesicles released from prostate cancer cells and cells of the tumour microenvironment carry molecular information about the disease that can be analysed in several biological fluids. Numerous studies document the interest of researchers in this field of research. However, methodological issues such as the isolation of vesicles have been challenging. Remarkably, novel technologies, including those based on nanotechnology, show promise for the further development and clinical use of extracellular vesicles as liquid biomarkers. Development of biomarkers is a long and complicated process, and there are still not many biomarkers based on extracellular vesicles in clinical use. However, the knowledge acquired during the last decade constitutes a solid basis for the future development of liquid biopsy tests for prostate cancer. These are urgently needed to bring prostate cancer treatment to the next level in precision medicine.
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Affiliation(s)
- Manuel Ramirez-Garrastacho
- Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | | | - Aija Line
- Latvian Biomedical Research and Study Centre, Riga, Latvia
| | - Elena S Martens-Uzunova
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Urology, Laboratory of Experimental Urology, Erasmus MC, Rotterdam, The Netherlands
| | - Jesus Martinez de la Fuente
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain
| | - Maria Moros
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain
| | - Carolina Soekmadji
- Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Kristin Austlid Tasken
- Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Alicia Llorente
- Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
- Department for Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway.
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34
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Chiangjong W, Netsirisawan P, Hongeng S, Chutipongtanate S. Red Blood Cell Extracellular Vesicle-Based Drug Delivery: Challenges and Opportunities. Front Med (Lausanne) 2021; 8:761362. [PMID: 35004730 PMCID: PMC8739511 DOI: 10.3389/fmed.2021.761362] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 12/06/2021] [Indexed: 12/29/2022] Open
Abstract
Recently, red blood cell-derived extracellular vesicles (RBCEVs) have attracted attention for clinical applications because of their safety and biocompatibility. RBCEVs can escape macrophages through the binding of CD47 to inhibitory receptor signal regulatory protein α. Furthermore, genetic materials such as siRNA, miRNA, mRNA, or single-stranded RNA can be encapsulated within RBCEVs and then released into target cells for precise treatment. However, their side effects, half-lives, target cell specificity, and limited large-scale production under good manufacturing practice remain challenging. In this review, we summarized the biogenesis and composition of RBCEVs, discussed the advantages and disadvantages of RBCEVs for drug delivery compared with synthetic nanovesicles and non-red blood cell-derived EVs, and provided perspectives for overcoming current limitations to the use of RBCEVs for clinical applications.
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Affiliation(s)
- Wararat Chiangjong
- Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pukkavadee Netsirisawan
- Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Suradej Hongeng
- Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Somchai Chutipongtanate
- Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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35
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Olmedillas-López S, Olivera-Salazar R, García-Arranz M, García-Olmo D. Current and Emerging Applications of Droplet Digital PCR in Oncology: An Updated Review. Mol Diagn Ther 2021; 26:61-87. [PMID: 34773243 DOI: 10.1007/s40291-021-00562-2] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2021] [Indexed: 12/14/2022]
Abstract
In the era of personalized medicine and targeted therapies for the management of patients with cancer, ultrasensitive detection methods for tumor genotyping, such as next-generation sequencing or droplet digital polymerase chain reaction (ddPCR), play a significant role. In the search for less invasive strategies for diagnosis, prognosis and disease monitoring, the number of publications regarding liquid biopsy approaches using ddPCR has increased substantially in recent years. There is a long list of malignancies in which ddPCR provides a reliable and accurate tool for detection of nucleic acid-based markers derived from cell-free DNA, cell-free RNA, circulating tumor cells, extracellular vesicles or exosomes when isolated from whole blood, plasma and serum, helping to anticipate tumor relapse or unveil intratumor heterogeneity and clonal evolution in response to treatment. This updated review describes recent developments in ddPCR platforms and provides a general overview about the major applications of liquid biopsy in blood, including its utility for molecular response and minimal residual disease monitoring in hematological malignancies or the therapeutic management of patients with colorectal or lung cancer, particularly for the selection and monitoring of treatment with tyrosine kinase inhibitors. Although plasma is the main source of genetic material for tumor genomic profiling, liquid biopsy by ddPCR is being investigated in a wide variety of biologic fluids, such as cerebrospinal fluid, urine, stool, ocular fluids, sputum, saliva, bronchoalveolar lavage, pleural effusion, mucin, peritoneal fluid, fine needle aspirate, bile or pancreatic juice. The present review focuses on these "alternative" sources of genetic material and their analysis by ddPCR in different kinds of cancers.
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Affiliation(s)
- Susana Olmedillas-López
- New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain.
| | - Rocío Olivera-Salazar
- New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain
| | - Mariano García-Arranz
- New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain.,Department of Surgery, School of Medicine, Universidad Autónoma de Madrid (UAM), 28029, Madrid, Spain
| | - Damián García-Olmo
- New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain.,Department of Surgery, School of Medicine, Universidad Autónoma de Madrid (UAM), 28029, Madrid, Spain.,Department of Surgery, Fundación Jiménez Díaz University Hospital (FJD), 28040, Madrid, Spain
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36
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Xu L, Liang Y, Xu X, Xia J, Wen C, Zhang P, Duan L. Blood cell-derived extracellular vesicles: diagnostic biomarkers and smart delivery systems. Bioengineered 2021; 12:7929-7940. [PMID: 34622717 PMCID: PMC8806567 DOI: 10.1080/21655979.2021.1982320] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Extracellular vesicles (EVs) are released by most of the cells or tissues and act as nanocarriers to transfer nucleic acids, proteins, and lipids. The blood system is the most abundant source of extracellular vesicles for purification, and it has attracted considerable attention as a source of diagnostic biomarkers. Blood-derived extracellular vesicles, especially vesicles released from erythrocytes and platelets, are highly important in nanoplatform-based therapeutic interventions as potentially ideal drug delivery vehicles. We reviewed the latest research progress on the paracrine effects and biological functions of extracellular vesicles derived from erythrocytes, leukocytes, platelets, and plasma. From a clinical perspective, we summarize selected useful diagnostic biomarkers for therapeutic intervention and diagnosis. Especially, we describe and discuss the potential application of erythrocyte-derived extracellular vesicles as a new nano-delivery platform for the desired therapeutics. We suggest that blood-derived extracellular vesicles are an ideal nanoplatform for disease diagnosis and therapy.
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Affiliation(s)
- Limei Xu
- Department of Orthopedics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Yujie Liang
- Department of Orthopedics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Xiao Xu
- Department of Orthopedics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Jiang Xia
- Department of Chemistry, and Center for Cell & Developmental Biology, School of Life Sciences, the Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Caining Wen
- Department of Orthopedics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China
| | - Peng Zhang
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Li Duan
- Department of Orthopedics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.,Shenzhen Institute of Geriatrics, Shenzhen, Guangdong Province, China
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37
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Exosomes as A Next-Generation Diagnostic and Therapeutic Tool in Prostate Cancer. Int J Mol Sci 2021; 22:ijms221810131. [PMID: 34576294 PMCID: PMC8465219 DOI: 10.3390/ijms221810131] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/15/2021] [Accepted: 09/16/2021] [Indexed: 12/03/2022] Open
Abstract
Extracellular vesicles (EVs) have brought great momentum to the non-invasive liquid biopsy procedure for the detection, characterization, and monitoring of cancer. Despite the common use of PSA (prostate-specific antigen) as a biomarker for prostate cancer, there is an unmet need for a more specific diagnostic tool to detect tumor progression and recurrence. Exosomes, which are EVs that are released from all cells, play a large role in physiology and pathology, including cancer. They are involved in intercellular communication, immune function, and they are present in every bodily fluid studied—making them an excellent window into how cells are operating. With liquid biopsy, EVs can be isolated and analyzed, enabling an insight into a potential therapeutic value, serving as a vehicle for drugs or nucleic acids that have anti-neoplastic effects. The current application of advanced technology also points to higher-sensitivity detection methods that are minimally invasive. In this review, we discuss the current understanding of the significance of exosomes in prostate cancer and the potential diagnostic value of these EVs in disease progression.
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Kim CJ, Dong L, Amend SR, Cho YK, Pienta KJ. The role of liquid biopsies in prostate cancer management. LAB ON A CHIP 2021; 21:3263-3288. [PMID: 34346466 DOI: 10.1039/d1lc00485a] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Liquid biopsy has emerged as a complement to invasive tissue biopsy to guide cancer diagnosis and treatment. The common liquid biopsy biomarkers are circulating tumor cells (CTCs), extracellular vesicles (EVs), and circulating tumor DNA (ctDNA). Each biomarker provides specific information based on its intrinsic characteristics. Prostate cancer is the second most common cancer in males worldwide. In men with low-grade localized prostate cancer, the disease can often be managed by active surveillance. For men who require treatment, the 5-year survival rate of localized prostate cancer is the highest among all cancer types, but the metastatic disease remains incurable. Metastatic prostate cancer invariably progresses to involve multiple bone sites and develops into a castration-resistant disease that leads to cancer death. The need to appropriately diagnose and guide the serial treatment of men with prostate cancer has led to the implementation of many studies to apply liquid biopsies to prostate cancer management. This review describes recent advancements in isolation and detection technology and the strength and weaknesses of the three circulating biomarkers. The clinical studies based on liquid biopsy results are summarized to depict the future perspective in the role of liquid biopsy on prostate cancer management.
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Affiliation(s)
- Chi-Ju Kim
- The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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Peng L, Li X, Li Y, Zhao W, Nie S, Yu H, Qi Y, Qin Y, Zhang H. Increased concentrations of myeloperoxidase in serum and serum extracellular vesicles are associated with type 2 diabetes mellitus. Clin Chim Acta 2021; 522:70-76. [PMID: 34390687 DOI: 10.1016/j.cca.2021.08.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/31/2021] [Accepted: 08/09/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Inflammatory response plays a critical role in the initiation and progression of type 2 diabetes mellitus (T2DM). Myeloperoxidase (MPO), a leukocyte-derived protagonist, exerts its proinflammatory properties in many complications. We explored the associations between serum extracellular vesicle (EV)-derived MPO as well as serum MPO and T2DM. METHODS We performed a cross-sectional study in 151 individuals, including 93 patients with T2DM and 58 non-T2DM controls. The concentrations of serum EV-derived MPO and serum MPO were measured by Luminex Assay. RESULTS Our data showed that serum EV-derived MPO concentrations and serum MPO concentrations were significantly higher in T2DM patients compared with non-T2DM subjects. In addition, multivariate logistic regression analysis revealed that serum EV-derived MPO as well as serum MPO was independently associated with the presence of T2DM even after adjusting for confounding factors (OR = 1.836 /1 ng EV-derived MPO, 95% CI = 1.395-2.417, P < 0.001; OR = 4.135 /10 ng serum MPO, 95% CI = 2.285-7.483, P < 0.001). Furthermore, serum MPO showed marginally higher discriminatory accuracy than serum EV-derived MPO in screening T2DM (AUC = 0.858; AUC = 0.779). CONCLUSION Increased concentrations of the inflammatory marker MPO either in serum or in serum EVs were independently associated with T2DM.
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Affiliation(s)
- Lu Peng
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xinwei Li
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yu Li
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Wen Zhao
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Shaoping Nie
- Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, China
| | - Huahui Yu
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yue Qi
- Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education; Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Yanwen Qin
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Huina Zhang
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
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Exosomes and prostate cancer management. Semin Cancer Biol 2021; 86:101-111. [PMID: 34384877 DOI: 10.1016/j.semcancer.2021.08.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/26/2021] [Accepted: 08/08/2021] [Indexed: 12/14/2022]
Abstract
Exosomes (and other extracellular vesicles) are now part of the cancer research landscape, involved both as players in pathophysiological mechanisms, as biomarkers of the cancer process and as therapeutic tools. One step they have yet to take is to move into routine clinical practice and management of prostate cancer is an example of this necessary maturation. More than for many other cancers and because a possible alternative is active surveillance (neither removal nor destruction), the diagnosis of prostate cancer does not only involve the detection of cancerous cells but also the determination of its true aggressiveness. By measuring TRMPRSS2:ERG fusion and PCA3 transcripts in urine exosomes, the EPI assay seems able to help prostate biopsy decision. Results from clinical studies showed that it can reduce the proportion of unnecessary biopsies while missing only a minimal proportion of clinically significant cancers. In metastatic prostate cancer, after failure of a first step androgen deprivation therapy, when a choice has to be made between a second-generation androgen receptor (AR) signaling inhibitor and taxane-based chemotherapy, detection of the AR splicing variant AR-V7 in circulating tumor cells (CTCs) has appeared promising. Whether exosomes could be a better material (simpler to isolate from the bloodstream than CTCs?) to detect AR-V7 has been suggested by some studies and remains to be confirmed. At last, a couple of exploratory studies either targeted or used exosomes to treat prostate cancer, by respectively inhibiting their secretion (to prevent exosome-mediated transfer of biologically active oncogenic actors), or loading them with immunogenic cancer-specific proteins (to generate anticancer vaccine) or with pharmacologic agents. Overall efforts are however still needed to confirm these results and generalize exosome-based diagnostic, prognostic or therapeutic strategies in prostate cancer management.
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Zhang L, Ding L, Li Y, Zhang F, Xu Y, Pan H, Wan X, Yan G, Yu F, Li R. EHD3 positively regulated by NR5A1 participates in testosterone synthesis via endocytosis. Life Sci 2021; 278:119570. [PMID: 33964295 DOI: 10.1016/j.lfs.2021.119570] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/19/2021] [Accepted: 04/25/2021] [Indexed: 01/23/2023]
Abstract
AIMS Increasing evidence has shown that hormone secretion is regulated by endocytosis. Eps15 homology domain-containing protein 3 (EHD3) is an endocytic-trafficking regulatory protein, but whether EHD3 is associated with testosterone secretion is not clear. This work aims to explore the role of EHD3 in testosterone synthesis. MAIN METHODS Testosterone concentration was determined by ELISA. The effects of EHD3 on endocytosis were assessed by exosomes tracing assay and Immunofluorescence. Targeting relationship between EHD3 and NR5A1 was verified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assay in Leydig cells. For in vivo assessments, conditional NR5A1 knockout mouse model was established with CRISPR/Cas9 gene targeting technology. KEY FINDINGS EHD3 overexpression significantly increased the concentration of testosterone. EHD3 knockdown markedly decreased testosterone synthesis by reducing endocytosis. The activity of the EHD3 promoter was positively regulated by NR5A1, which occupied the conserved sequence "AGGTCA" in the EHD3 promoter. Furthermore, mice with a Leydig cell-specific conditional NR5A1 knockout displayed the blunted levels of EHD3 and clathrin (a key factor for endocytosis), and serum testosterone concentration compared with NR5A1f/f mice. SIGNIFICANCE This study suggests a potential molecular mechanism of testosterone synthesis to fully understand male reproductive health.
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Affiliation(s)
- Lingling Zhang
- NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Pharmacy, Fudan University, Shanghai 200032, China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China; Center for Reproductive Medicine, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing 210008, China; Center for Molecular Reproductive Medicine, Nanjing University, Nanjing 210008, China
| | - Lijun Ding
- Center for Reproductive Medicine, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing 210008, China; Center for Molecular Reproductive Medicine, Nanjing University, Nanjing 210008, China; Clinical Center for Stem Cell Research, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Yifan Li
- Center for Reproductive Medicine, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing 210008, China; Center for Molecular Reproductive Medicine, Nanjing University, Nanjing 210008, China
| | - Fangxi Zhang
- NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Pharmacy, Fudan University, Shanghai 200032, China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China
| | - Yanhong Xu
- Center for Reproductive Medicine, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing 210008, China; Center for Molecular Reproductive Medicine, Nanjing University, Nanjing 210008, China
| | - Hongjie Pan
- NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China
| | - Xiaofeng Wan
- NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China
| | - Guijun Yan
- Center for Reproductive Medicine, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing 210008, China; Center for Molecular Reproductive Medicine, Nanjing University, Nanjing 210008, China
| | - Fei Yu
- Center for Experimental Animal, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
| | - Runsheng Li
- NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Pharmacy, Fudan University, Shanghai 200032, China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China.
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Saldana C, Majidipur A, Beaumont E, Huet E, de la Taille A, Vacherot F, Firlej V, Destouches D. Extracellular Vesicles in Advanced Prostate Cancer: Tools to Predict and Thwart Therapeutic Resistance. Cancers (Basel) 2021; 13:cancers13153791. [PMID: 34359692 PMCID: PMC8345194 DOI: 10.3390/cancers13153791] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/21/2021] [Accepted: 07/23/2021] [Indexed: 02/07/2023] Open
Abstract
Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death among men worldwide. At first, advanced PCa is treated by androgen deprivation therapy with a good initial response. Nevertheless, recurrences occur, leading to Castrate-Resistance Prostate Cancer (CRPC). During the last decade, new therapies based on inhibition of the androgen receptor pathway or taxane chemotherapies have been used to treat CRPC patients leading to an increase in overall survival, but the occurrence of resistances limits their benefits. Numerous studies have demonstrated the implication of extracellular vesicles (EVs) in different cancer cellular mechanisms. Thus, the possibility to isolate and explore EVs produced by tumor cells in plasma/sera represents an important opportunity for the deciphering of those mechanisms and the discovery of biomarkers. Herein, we summarized the role of EVs in therapeutic resistance of advanced prostate cancer and their use to find biomarkers able to predict these resistances.
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Affiliation(s)
- Carolina Saldana
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
- AP-HP, Hopital Henri-Mondor, Service Oncologie, F-94010 Creteil, France
| | - Amene Majidipur
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
| | - Emma Beaumont
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
| | - Eric Huet
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
| | - Alexandre de la Taille
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
- AP-HP, Hopital Henri-Mondor, Service Urologie, F-94010 Creteil, France
| | - Francis Vacherot
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
| | - Virginie Firlej
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
| | - Damien Destouches
- Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France; (C.S.); (A.M.); (E.B.); (E.H.); (A.d.l.T.); (F.V.); (V.F.)
- Correspondence: ; Tel.: +33-(0)1-49-81-36-14; Fax: +33-(0)1-49-81-39-00
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Bordanaba-Florit G, Royo F, Kruglik SG, Falcón-Pérez JM. Using single-vesicle technologies to unravel the heterogeneity of extracellular vesicles. Nat Protoc 2021; 16:3163-3185. [PMID: 34135505 DOI: 10.1038/s41596-021-00551-z] [Citation(s) in RCA: 167] [Impact Index Per Article: 41.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 03/31/2021] [Indexed: 12/12/2022]
Abstract
Extracellular vesicles (EVs) are heterogeneous lipid containers with a complex molecular cargo comprising several populations with unique roles in biological processes. These vesicles are closely associated with specific physiological features, which makes them invaluable in the detection and monitoring of various diseases. EVs play a key role in pathophysiological processes by actively triggering genetic or metabolic responses. However, the heterogeneity of their structure and composition hinders their application in medical diagnosis and therapies. This diversity makes it difficult to establish their exact physiological roles, and the functions and composition of different EV (sub)populations. Ensemble averaging approaches currently employed for EV characterization, such as western blotting or 'omics' technologies, tend to obscure rather than reveal these heterogeneities. Recent developments in single-vesicle analysis have made it possible to overcome these limitations and have facilitated the development of practical clinical applications. In this review, we discuss the benefits and challenges inherent to the current methods for the analysis of single vesicles and review the contribution of these approaches to the understanding of EV biology. We describe the contributions of these recent technological advances to the characterization and phenotyping of EVs, examination of the role of EVs in cell-to-cell communication pathways and the identification and validation of EVs as disease biomarkers. Finally, we discuss the potential of innovative single-vesicle imaging and analysis methodologies using microfluidic devices, which promise to deliver rapid and effective basic and practical applications for minimally invasive prognosis systems.
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Affiliation(s)
- Guillermo Bordanaba-Florit
- Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain.
| | - Félix Royo
- Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Madrid, Spain
| | - Sergei G Kruglik
- Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, Laboratoire Jean Perrin, Paris, France
| | - Juan M Falcón-Pérez
- Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain. .,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Madrid, Spain. .,Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
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Vaillancourt M, Hubert A, Subra C, Boucher J, Bazié WW, Vitry J, Berrazouane S, Routy JP, Trottier S, Tremblay C, Jenabian MA, Benmoussa A, Provost P, Tessier PA, Gilbert C. Velocity Gradient Separation Reveals a New Extracellular Vesicle Population Enriched in miR-155 and Mitochondrial DNA. Pathogens 2021; 10:526. [PMID: 33925397 PMCID: PMC8146806 DOI: 10.3390/pathogens10050526] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/10/2021] [Accepted: 04/20/2021] [Indexed: 12/18/2022] Open
Abstract
Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus (HIV-1) may provide insights into pathogenesis, inflammation, and disease progression. However, distinguishing plasma membrane EVs from exosomes, exomeres, apoptotic bodies, virions, and contaminating proteins remains challenging. We aimed at comparing sucrose and iodixanol density and velocity gradients along with commercial kits as a means of separating EVs from HIV particles and contaminating protein like calprotectin; and thereby evaluating the suitability of current plasma EVs analysis techniques for identifying new biomarkers of HIV-1 immune activation. Multiple analysis have been performed on HIV-1 infected cell lines, plasma from HIV-1 patients, or plasma from HIV-negative individuals spiked with HIV-1. Commercial kits, the differential centrifugation and density or velocity gradients to precipitate and separate HIV, EVs, and proteins such as calprotectin, have been used. EVs, virions, and contaminating proteins were characterized using Western blot, ELISA, RT-PCR, hydrodynamic size measurement, and enzymatic assay. Conversely to iodixanol density or velocity gradient, protein and virions co-sedimented in the same fractions of the sucrose density gradient than AChE-positive EVs. Iodixanol velocity gradient provided the optimal separation of EVs from viruses and free proteins in culture supernatants and plasma samples from a person living with HIV (PLWH) or a control and revealed a new population of large EVs enriched in microRNA miR-155 and mitochondrial DNA. Although EVs and their contents provide helpful information about several key events in HIV-1 pathogenesis, their purification and extensive characterization by velocity gradient must be investigated thoroughly before further use as biomarkers. By revealing a new population of EVs enriched in miR-155 and mitochondrial DNA, this study paves a way to increase our understanding of HIV-1 pathogenesis.
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Affiliation(s)
- Myriam Vaillancourt
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
| | - Audrey Hubert
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
| | - Caroline Subra
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Julien Boucher
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
| | - Wilfried Wenceslas Bazié
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
- Programme de Recherche sur les Maladies Infectieuses, Centre Muraz, Institut National de Santé Publique, Bobo-Dioulasso 01 BP 390, Burkina Faso
| | - Julien Vitry
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
| | - Sofiane Berrazouane
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
| | - Jean-Pierre Routy
- Chronic Viral Illness Service and Division of Hematology, McGill University Health Centre, Montréal, QC H4A 3J1, Canada;
- Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montréal, QC H4A 3J1, Canada
| | - Sylvie Trottier
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
- Centre de Recherche du CHU de Québec, Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada
| | - Cécile Tremblay
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, QC H3C 3J7, Canada;
- Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada
| | - Mohammad-Ali Jenabian
- Département des Sciences Biologiques et Centre de Recherche CERMO-FC, Université du Québec à Montréal (UQAM), Montréal, QC H2L 2C4, Canada;
| | - Abderrahim Benmoussa
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
- Department of Nutrition, CHU Sainte-Justine—Université de Montréal, Montréal, QC H3T 1J4, Canada
| | - Patrick Provost
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
- Centre de Recherche du CHU de Québec, Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada
| | - Philippe A. Tessier
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
- Centre de Recherche du CHU de Québec, Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada
| | - Caroline Gilbert
- Centre de Recherche du CHU de Québec-Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada; (M.V.); (A.H.); (C.S.); (J.B.); (W.W.B.); (J.V.); (S.B.); (S.T.); (A.B.); (P.P.); (P.A.T.)
- Centre de Recherche du CHU de Québec, Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université Laval, T1-49, 2705 boulevard Laurier, Québec, QC G1V 4G2, Canada
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Balázs K, Antal L, Sáfrány G, Lumniczky K. Blood-Derived Biomarkers of Diagnosis, Prognosis and Therapy Response in Prostate Cancer Patients. J Pers Med 2021; 11:296. [PMID: 33924671 PMCID: PMC8070149 DOI: 10.3390/jpm11040296] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 03/31/2021] [Accepted: 04/03/2021] [Indexed: 12/11/2022] Open
Abstract
Prostate cancer is among the most frequent cancers in men worldwide. Despite the fact that multiple therapeutic alternatives are available for its treatment, it is often discovered in an advanced stage as a metastatic disease. Prostate cancer screening is based on physical examination of prostate size and prostate-specific antigen (PSA) level in the blood as well as biopsy in suspect cases. However, these markers often fail to correctly identify the presence of cancer, or their positivity might lead to overdiagnosis and consequent overtreatment of an otherwise silent non-progressing disease. Moreover, these markers have very limited if any predictive value regarding therapy response or individual risk for therapy-related toxicities. Therefore, novel, optimally liquid biopsy-based (blood-derived) markers or marker panels are needed, which have better prognostic and predictive value than the ones currently used in the everyday routine. In this review the role of circulating tumour cells, extracellular vesicles and their microRNA content, as well as cellular and soluble immunological and inflammation- related blood markers for prostate cancer diagnosis, prognosis and prediction of therapy response is discussed. A special emphasis is placed on markers predicting response to radiotherapy and radiotherapy-related late side effects.
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Affiliation(s)
| | | | | | - Katalin Lumniczky
- Unit of Radiation Medicine, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, Hungary; (K.B.); (L.A.); (G.S.)
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Hatano K, Fujita K. Extracellular vesicles in prostate cancer: a narrative review. Transl Androl Urol 2021; 10:1890-1907. [PMID: 33968677 PMCID: PMC8100827 DOI: 10.21037/tau-20-1210] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Over the past decade, there has been remarkable progress in prostate cancer biomarker discovery using urine- and blood-based assays. A liquid biopsy is a minimally invasive procedure to investigate the cancer-related molecules in circulating tumor cells (CTCs), cell-free DNA, and extracellular vesicles (EVs). Liquid biopsies have the advantage of detecting heterogeneity as well as acquired resistance in cancer. EVs are cell-derived vesicles enclosed by a lipid bilayer and contain various molecules, such as nucleic acids, proteins, and lipids. In patients with cancer, EVs derived from tumors can be isolated from urine, plasma, and serum. The advances in isolation techniques provide the opportunity to use EVs as biomarkers in the clinic. Emerging evidence suggests that EVs can be useful biomarkers for the diagnosis of prostate cancer, especially high-grade cancer. EVs can also be potent biomarkers for the prediction of disease progression in patients with castration-resistant prostate cancer (CRPC). EVs shed from cancer and stromal cells are involved in the development of tumor microenvironments, enhancing cancer progression, metastasis, and drug resistance. Here, we provide an overview of the use of EVs for the diagnosis of clinically significant prostate cancer as well as for predicting disease progression. We also discuss the biological function of EVs, which regulate cancer progression.
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Affiliation(s)
- Koji Hatano
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kazutoshi Fujita
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.,Department of Urology, Kindai University Faculty of Medicine, Osakasayama, Japan
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Kurian TK, Banik S, Gopal D, Chakrabarti S, Mazumder N. Elucidating Methods for Isolation and Quantification of Exosomes: A Review. Mol Biotechnol 2021; 63:249-266. [PMID: 33492613 PMCID: PMC7940341 DOI: 10.1007/s12033-021-00300-3] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2021] [Indexed: 12/14/2022]
Abstract
Exosomes are the smallest extracellular vesicles present in most of the biological fluids. They are found to play an important role in cell signaling, immune response, tumor metastasis, etc. Studies have shown that these vesicles also have diagnostic and therapeutic roles for which their accurate detection and quantification is essential. Due to the complexity in size and structure of exosomes, even the gold standard methods face challenges. This comprehensive review discusses the various standard methods such as ultracentrifugation, ultrafiltration, size-exclusion chromatography, precipitation, immunoaffinity, and microfluidic technologies for the isolation of exosomes. The principle of isolation of each method is described, as well as their specific advantages and disadvantages. Quantification of exosomes by nanoparticle tracking analysis, flow cytometry, tunable resistive pulse sensing, electron microscopy, dynamic light scattering, and microfluidic devices are also described, along with the applications of exosomes in various biomedical domains.
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Affiliation(s)
- Talitha Keren Kurian
- Department of Biophysics, Manipal School of Life Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104 India
| | - Soumyabrata Banik
- Department of Biophysics, Manipal School of Life Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104 India
| | - Dharshini Gopal
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104 India
| | - Shweta Chakrabarti
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104 India
| | - Nirmal Mazumder
- Department of Biophysics, Manipal School of Life Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104 India
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Akoto T, Saini S. Role of Exosomes in Prostate Cancer Metastasis. Int J Mol Sci 2021; 22:3528. [PMID: 33805398 PMCID: PMC8036381 DOI: 10.3390/ijms22073528] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 03/22/2021] [Accepted: 03/26/2021] [Indexed: 02/06/2023] Open
Abstract
Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.
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Affiliation(s)
- Theresa Akoto
- Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA;
| | - Sharanjot Saini
- Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA
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Zhao Y, Chen Y, Wang J, Liu L. Effects of ATP-binding cassette transporter G2 in extracellular vesicles on drug resistance of laryngeal cancer cells in in vivo and in vitro. Oncol Lett 2021; 21:364. [PMID: 33747221 DOI: 10.3892/ol.2021.12625] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 02/16/2021] [Indexed: 01/21/2023] Open
Abstract
Drug resistance is one of the main factors limiting the efficacy of chemotherapy in patients with laryngeal cancer; thus, it is important to investigate the drug resistance of laryngeal cancer. In the present study, the mechanism of the regulation of drug resistance in laryngeal cancer cells by ATP-binding transporter G2 (ABCG2) that is present in the extracellular vesicles (EVs) released by drug-resistant cells was studied in vivo and in vitro. A cisplatin (CDDP)-resistant cell line (AMC-HN-8/CDDP) was established from AMC-HN-8 cells by continuous exposure to increasing concentrations of CDDP. The EVs extracted from the culture medium of AMC-HN-8/CDDP and AMC-HN-8 cells were termed EVs1 and EVs2, respectively. Following 48-h treatment of AMC-HN-8 cells with EVs1 or EVs2, the cells were designated as AMC-HN-8-EVs1 or AMC-HN-8-EVs2. Nude mice bearing AMC-HN-8-EVs1 and AMC-HN-8 cell-derived xenograft tumors were established to detect the effects of EVs on drug resistance. The resistance index of AMC-HN-8/CDDP cells to CDDP was 5.60, which was determined by the MTT assay. The mRNA and protein expression levels of ABCG2 in AMC-HN-8/CDDP cells and EVs1 were significantly higher compared with those in AMC-HN-8 cells and EVs2, respectively (P<0.01). The ABCG2 mRNA and protein levels, and the proliferation index of AMC-HN-8-EVs1 cells were significantly higher compared with those of AMC-HN-8-EVs2 and AMC-HN-8 cells (P<0.01), whereas the apoptotic rate was significantly lower (P<0.01). The mean volume of subcutaneous tumor xenografts in the test group (inoculated with AMC-HN-8-EVs1 cells and intraperitoneally injected with 3 mg/kg CDDP) was significantly higher compared with that in the control group (inoculated with AMC-HN-8 cells and intraperitoneally injected with 3 mg/kg CDDP) (P<0.01), whereas the apoptotic rate of tumor cells was significantly lower (P<0.01). The ABCG2 mRNA and the protein expression levels in the tumor cells of the test group were significantly higher compared with those in the blank (inoculated with AMC-HN-8 cells and was intraperitoneally injected with normal saline) and control groups (P<0.01). The high expression levels of ABCG2 in laryngeal carcinoma cells affected the drug resistance of the cells. The EVs released by drug-resistant cells upregulated the expression of ABCG2 and induced drug resistance in laryngeal carcinoma cells, which may be dependent on the ABCG2 gene carried by the EVs.
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Affiliation(s)
- Yan Zhao
- Department of Otolaryngology, Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Yuetong Chen
- Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Jing Wang
- Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Liang Liu
- Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
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Bordanaba-Florit G, Madarieta I, Olalde B, Falcón-Pérez JM, Royo F. 3D Cell Cultures as Prospective Models to Study Extracellular Vesicles in Cancer. Cancers (Basel) 2021; 13:307. [PMID: 33467651 PMCID: PMC7830667 DOI: 10.3390/cancers13020307] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/10/2021] [Accepted: 01/12/2021] [Indexed: 12/12/2022] Open
Abstract
The improvement of culturing techniques to model the environment and physiological conditions surrounding tumors has also been applied to the study of extracellular vesicles (EVs) in cancer research. EVs role is not only limited to cell-to-cell communication in tumor physiology, they are also a promising source of biomarkers, and a tool to deliver drugs and induce antitumoral activity. In the present review, we have addressed the improvements achieved by using 3D culture models to evaluate the role of EVs in tumor progression and the potential applications of EVs in diagnostics and therapeutics. The most employed assays are gel-based spheroids, often utilized to examine the cell invasion rate and angiogenesis markers upon EVs treatment. To study EVs as drug carriers, a more complex multicellular cultures and organoids from cancer stem cell populations have been developed. Such strategies provide a closer response to in vivo physiology observed responses. They are also the best models to understand the complex interactions between different populations of cells and the extracellular matrix, in which tumor-derived EVs modify epithelial or mesenchymal cells to become protumor agents. Finally, the growth of cells in 3D bioreactor-like systems is appointed as the best approach to industrial EVs production, a necessary step toward clinical translation of EVs-based therapy.
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Affiliation(s)
- Guillermo Bordanaba-Florit
- Center for Cooperative Research in Biosciences (CIC bioGUNE), Exosomes Laboratory, Basque Research and Technology Alliance (BRTA), E48160 Derio, Spain; (G.B.-F.); (J.M.F.-P.)
| | - Iratxe Madarieta
- TECNALIA Basque Research and Technology Alliance (BRTA), E20009 Donostia San Sebastian, Spain; (I.M.); (B.O.)
| | - Beatriz Olalde
- TECNALIA Basque Research and Technology Alliance (BRTA), E20009 Donostia San Sebastian, Spain; (I.M.); (B.O.)
| | - Juan M. Falcón-Pérez
- Center for Cooperative Research in Biosciences (CIC bioGUNE), Exosomes Laboratory, Basque Research and Technology Alliance (BRTA), E48160 Derio, Spain; (G.B.-F.); (J.M.F.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), E28029 Madrid, Spain
- Ikerbasque, Basque Foundation for Science, E48009 Bilbao, Spain
| | - Félix Royo
- Center for Cooperative Research in Biosciences (CIC bioGUNE), Exosomes Laboratory, Basque Research and Technology Alliance (BRTA), E48160 Derio, Spain; (G.B.-F.); (J.M.F.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), E28029 Madrid, Spain
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