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Acharya SK, Shai S, Choon YF, Gunardi I, Hartanto FK, Kadir K, Roychoudhury A, Amtha R, Vincent-Chong VK. Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges. Biomedicines 2024; 12:2111. [PMID: 39335624 PMCID: PMC11429394 DOI: 10.3390/biomedicines12092111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 09/11/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
Cancer stem cells (CSCs) represent a subpopulation of cancer cells that are believed to initiate and drive cancer progression. In animal models, xenotransplanted CSCs have demonstrated the ability to produce tumors. Since their initial isolation in blood cancers, CSCs have been identified in various solid human cancers, including oral squamous cell carcinoma (OSCC). In addition to their tumorigenic properties, dysregulated stem-cell-related signaling pathways-Wnt family member (Wnt), neurogenic locus notch homolog protein (Notch), and hedgehog-have been shown to endow CSCs with characteristics like self-renewal, phenotypic plasticity, and chemoresistance, contributing to recurrence and treatment failure. Consequently, CSCs have become targets for new therapeutic agents, with some currently in different phases of clinical trials. Notably, small molecule inhibitors of the hedgehog signaling pathway, such as vismodegib and glasdegib, have been approved for the treatment of basal cell carcinoma and acute myeloid leukemia, respectively. Other strategies for eradicating CSCs include natural compounds, nano-drug delivery systems, targeting mitochondria and the CSC microenvironment, autophagy, hyperthermia, and immunotherapy. Despite the extensive documentation of CSCs in OSCC since its first demonstration in head and neck (HN) SCC in 2007, none of these novel pharmacological approaches have yet entered clinical trials for OSCC patients. This narrative review summarizes the in vivo and in vitro evidence of CSCs and CSC-related signaling pathways in OSCC, highlighting their role in promoting chemoresistance and immunotherapy resistance. Additionally, it addresses methodological challenges and discusses future research directions to improve experimental systems and advance CSC studies.
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Affiliation(s)
- Surendra Kumar Acharya
- Department of Oral Medicine, Radiology and Surgery, Faculty of Dentistry, Lincoln University College, Petaling Jaya 47301, Selangor, Malaysia
| | - Saptarsi Shai
- Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX 77030, USA;
| | - Yee Fan Choon
- Department of Oral and Maxillofacial Surgical Sciences, Faculty of Dentistry, MAHSA University, Jenjarom 42610, Selangor, Malaysia;
| | - Indrayadi Gunardi
- Oral Medicine Department, Faculty of Dentistry, Universitas Trisakti, Jakarta 11440, Indonesia; (I.G.); (F.K.H.)
| | - Firstine Kelsi Hartanto
- Oral Medicine Department, Faculty of Dentistry, Universitas Trisakti, Jakarta 11440, Indonesia; (I.G.); (F.K.H.)
| | - Kathreena Kadir
- Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia;
| | - Ajoy Roychoudhury
- Department of Oral and Maxillofacial Surgery, All India Institute of Medical Sciences, New Delhi 110029, India;
| | - Rahmi Amtha
- Oral Medicine Department, Faculty of Dentistry, Universitas Trisakti, Jakarta 11440, Indonesia; (I.G.); (F.K.H.)
| | - Vui King Vincent-Chong
- Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
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Loda A, Semeraro F, Parolini S, Ronca R, Rezzola S. Cancer stem-like cells in uveal melanoma: novel insights and therapeutic implications. Biochim Biophys Acta Rev Cancer 2024; 1879:189104. [PMID: 38701937 DOI: 10.1016/j.bbcan.2024.189104] [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: 02/14/2024] [Revised: 04/24/2024] [Accepted: 04/27/2024] [Indexed: 05/06/2024]
Abstract
Uveal melanoma (UM) is the most common primary ocular tumor in the adult population. Even though these primary tumors are successfully treated in 90% of cases, almost 50% of patients ultimately develop metastasis, mainly in the liver, via hematological dissemination, with a median survival spanning from 6 to 12 months after diagnosis. In this context, chemotherapy regimens and molecular targeted therapies have demonstrated poor response rates and failed to improve survival. Among the multiple reasons for therapy failure, the presence of cancer stem-like cells (CSCs) represents the main cause of resistance to anticancer therapies. In the last few years, the existence of CSCs in UM has been demonstrated both in preclinical and clinical studies, and new molecular pathways and mechanisms have been described for this subpopulation of UM cells. Here, we will discuss the state of the art of CSC biology and their potential exploitation as therapeutic target in UM.
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Affiliation(s)
- Alessandra Loda
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Francesco Semeraro
- Eye Clinic, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Silvia Parolini
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; National Center for Gene Therapy and Drugs based on RNA Technology - CN3, Padova, Italy; Consorzio Interuniversitario per le Biotecnologie (CIB), Italy
| | - Roberto Ronca
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Consorzio Interuniversitario per le Biotecnologie (CIB), Italy
| | - Sara Rezzola
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
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Bi Y, Zhang L, Song Y, Sun L, Mulholland MW, Yin Y, Zhang W. Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/β-catenin signaling pathway. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:352-365. [PMID: 37437654 PMCID: PMC10863972 DOI: 10.1016/j.gastrohep.2023.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 04/13/2023] [Accepted: 05/01/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. METHODS Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients' clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. RESULTS LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of β-catenin, whereas IWR-1, an inhibitor of Wnt/β-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of β-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. CONCLUSIONS LGR4 promotes HCC progression via Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Yanghui Bi
- School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Liping Zhang
- Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA
| | - Yan Song
- First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lijun Sun
- School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Michael W Mulholland
- Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA
| | - Yue Yin
- Department of Pharmacology, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University, Beijing, China.
| | - Weizhen Zhang
- School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.
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Moreira-Barbosa C, Matos A, Fernandes R, Mendes-Ferreira M, Rodrigues R, Cruz T, Costa ÂM, Cardoso AP, Ghilardi C, Oliveira MJ, Ribeiro R. The role of fatty acids metabolism on cancer progression and therapeutics development. BIOACTIVE LIPIDS 2023:101-132. [DOI: 10.1016/b978-0-12-824043-4.00007-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kciuk M, Gielecińska A, Budzinska A, Mojzych M, Kontek R. Metastasis and MAPK Pathways. Int J Mol Sci 2022; 23:ijms23073847. [PMID: 35409206 PMCID: PMC8998814 DOI: 10.3390/ijms23073847] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/18/2022] [Accepted: 03/29/2022] [Indexed: 02/07/2023] Open
Abstract
Cancer is a leading cause of death worldwide. In many cases, the treatment of the disease is limited due to the metastasis of cells to distant locations of the body through the blood and lymphatic drainage. Most of the anticancer therapeutic options focus mainly on the inhibition of tumor cell growth or the induction of cell death, and do not consider the molecular basis of metastasis. The aim of this work is to provide a comprehensive review focusing on cancer metastasis and the mitogen-activated protein kinase (MAPK) pathway (ERK/JNK/P38 signaling) as a crucial modulator of this process.
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Affiliation(s)
- Mateusz Kciuk
- Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
- Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 12/16 Banacha St., 90-237 Lodz, Poland; (A.G.); (R.K.)
- Correspondence:
| | - Adrianna Gielecińska
- Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 12/16 Banacha St., 90-237 Lodz, Poland; (A.G.); (R.K.)
| | - Adrianna Budzinska
- Laboratory of Mitochondrial Biochemistry, Department of Bioenergetics, Faculty of Biology, Adam Mickiewicz University, 61-614 Poznan, Poland;
| | - Mariusz Mojzych
- Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland;
| | - Renata Kontek
- Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 12/16 Banacha St., 90-237 Lodz, Poland; (A.G.); (R.K.)
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Banz-Jansen C, Helweg LP, Kaltschmidt B. Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go? Int J Mol Sci 2022; 23:ijms23063412. [PMID: 35328833 PMCID: PMC8955970 DOI: 10.3390/ijms23063412] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 03/08/2022] [Accepted: 03/19/2022] [Indexed: 02/04/2023] Open
Abstract
Endometrial cancer is one of the most common malignant diseases in women worldwide, with an incidence of 5.9%. Thus, it is the most frequent cancer of the female genital tract, with more than 34,000 women dying, in Europe and North America alone. Endometrial Cancer Stem Cells (CSC) might be drivers of carcinogenesis as well as metastatic and recurrent disease. Therefore, targeting CSCs is of high interest to improve prognosis of patients suffering of advanced or recurrent endometrial cancer. This review describes the current evidence of molecular mechanisms in endometrial CSCs with special emphasis on MYC and NF-κB signaling as well as mitochondrial metabolism. Furthermore, the current status of immunotherapy targeting PD-1 and PD-L1 in endometrial cancer cells and CSCs is elucidated. The outlined findings encourage novel therapies that target signaling pathways in endometrial CSCs as well as immunotherapy as a promising therapeutic approach in the treatment of endometrial cancer to impede cancer progression and prevent recurrence.
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Affiliation(s)
- Constanze Banz-Jansen
- Department of Gynecology and Obstetrics, and Perinatal Center, Protestant Hospital of Bethel Foundation, University Medical School OWL at Bielefeld, Bielefeld University, Campus Bielefeld-Bethel, Burgsteig 13, 33617 Bielefeld, Germany;
- Forschungsverbund BioMedizin Bielefeld, OWL (FBMB e.V.), Maraweg 21, 33617 Bielefeld, Germany;
| | - Laureen P. Helweg
- Forschungsverbund BioMedizin Bielefeld, OWL (FBMB e.V.), Maraweg 21, 33617 Bielefeld, Germany;
- Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany
- Correspondence:
| | - Barbara Kaltschmidt
- Forschungsverbund BioMedizin Bielefeld, OWL (FBMB e.V.), Maraweg 21, 33617 Bielefeld, Germany;
- Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany
- Molecular Neurobiology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany
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Zou W, Zhang Y, Bai G, Zhuang J, Wei L, Wang Z, Sun M, Wang J. siRNA-induced CD44 knockdown suppresses the proliferation and invasion of colorectal cancer stem cells through inhibiting epithelial-mesenchymal transition. J Cell Mol Med 2022; 26:1969-1978. [PMID: 35229451 PMCID: PMC8980945 DOI: 10.1111/jcmm.17221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 01/15/2022] [Accepted: 01/18/2022] [Indexed: 12/04/2022] Open
Abstract
CD44 has shown prognostic values and promising therapeutic potential in multiple human cancers; however, the effects of CD44 silencing on biological behaviors of cancer stem cells (CSCs) have not been fully understood in colorectal cancer. To examine the contribution of siRNA‐induced knockdown of CD44 to the biological features of colorectal CSCs, colorectal CSCs HCT116‐CSCs were generated, and CD44 was knocked down in HCT116‐CSCs using siRNA. The proliferation, migration and invasion of HCT116‐CSCs were measured, and apoptosis and cell‐cycle analyses were performed. The sensitivity of HCT116‐CSCs to oxaliplatin was tested, and xenograft tumor growth assay was performed to examine the role of CD44 in HCT116‐CSCs tumorigenesis in vivo. In addition, the expression of epithelial–mesenchymal transition (EMT) markers E‐cadherin, N‐cadherin and vimentin was quantified. siRNA‐induced knockdown of CD44 was found to inhibit the proliferation, migration and invasion, induce apoptosis, promote cell‐cycle arrest at the G1/G0 phase and increase the sensitivity of HCT116‐CSCs to oxaliplatin in HCT116‐CSCs, and knockdown of CD44 suppressed in vivo tumorigenesis and intrapulmonary metastasis of HCT116‐CSCs. Moreover, silencing CD44 resulted in EMT inhibition. Our findings demonstrate that siRNA‐induced CD44 knockdown suppresses the proliferation, invasion and in vivo tumorigenesis and metastasis of colorectal CSCs by inhibiting EMT.
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Affiliation(s)
- Weiyan Zou
- Department of Histology and Embryology, Bengbu Medical College, Bengbu City, China
| | - Yi Zhang
- The Second Department of Surgery, Xiamen Hospital Affiliated to Beijing University of Chinese Medicine, Xiamen City, China
| | - Guangfu Bai
- Department of Emergency, Wuxi Huishan District People's Hospital, Wuxi City, China
| | - Jialu Zhuang
- The Second School of Clinical Medicine, Bengbu Medical College, Bengbu City, China
| | - Lin Wei
- The Second School of Clinical Medicine, Bengbu Medical College, Bengbu City, China
| | - Zishu Wang
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, China
| | - Meiqun Sun
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, China
| | - Junbin Wang
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, China
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Arjmand B, Hamidpour SK, Alavi-Moghadam S, Yavari H, Shahbazbadr A, Tavirani MR, Gilany K, Larijani B. Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes. Front Pharmacol 2022; 13:768556. [PMID: 35264950 PMCID: PMC8899123 DOI: 10.3389/fphar.2022.768556] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 01/13/2022] [Indexed: 12/12/2022] Open
Abstract
Cancer stem cells (CSCs) are subpopulation of cells which have been demonstrated in a variety of cancer models and involved in cancer initiation, progression, and development. Indeed, CSCs which seem to form a small percentage of tumor cells, display resembling characteristics to natural stem cells such as self-renewal, survival, differentiation, proliferation, and quiescence. Moreover, they have some characteristics that eventually can demonstrate the heterogeneity of cancer cells and tumor progression. On the other hand, another aspect of CSCs that has been recognized as a central concern facing cancer patients is resistance to mainstays of cancer treatment such as chemotherapy and radiation. Owing to these details and the stated stemness capabilities, these immature progenitors of cancerous cells can constantly persist after different therapies and cause tumor regrowth or metastasis. Further, in both normal development and malignancy, cellular metabolism and stemness are intricately linked and CSCs dominant metabolic phenotype changes across tumor entities, patients, and tumor subclones. Hence, CSCs can be determined as one of the factors that correlate to the failure of common therapeutic approaches in cancer treatment. In this context, researchers are searching out new alternative or complementary therapies such as targeted methods to fight against cancer. Molecular docking is one of the computational modeling methods that has a new promise in cancer cell targeting through drug designing and discovering programs. In a simple definition, molecular docking methods are used to determine the metabolic interaction between two molecules and find the best orientation of a ligand to its molecular target with minimal free energy in the formation of a stable complex. As a comprehensive approach, this computational drug design method can be thought more cost-effective and time-saving compare to other conventional methods in cancer treatment. In addition, increasing productivity and quality in pharmaceutical research can be another advantage of this molecular modeling method. Therefore, in recent years, it can be concluded that molecular docking can be considered as one of the novel strategies at the forefront of the cancer battle via targeting cancer stem cell metabolic processes.
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Affiliation(s)
- Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- *Correspondence: Babak Arjmand, ; Bagher Larijani,
| | - Shayesteh Kokabi Hamidpour
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanieh Yavari
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ainaz Shahbazbadr
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Kambiz Gilany
- Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
- Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- *Correspondence: Babak Arjmand, ; Bagher Larijani,
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Zhou D, He Y, Li H, Huang W. KLK6 mediates stemness and metabolism of gastric carcinoma cells via the PI3K/AKT/mTOR signaling pathway. Oncol Lett 2021; 22:824. [PMID: 34691251 DOI: 10.3892/ol.2021.13085] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 04/23/2021] [Indexed: 01/02/2023] Open
Abstract
Gastric cancer is a common tumor of the digestive system, which can occur in any part of the stomach. Kallikrein 6 (KLK6) is a trypsin-like serine protease and has been found to be involved in extracellular matrix remodeling, tumor invasion and nervous system plasticity. Our previous study reported that KLK6 suppressed HGC-27 gastric cancer cell growth by inhibiting epithelial-mesenchymal transition; however, the mechanism of action underlying the effect of KLK6 still remains unclear. The aim of the present study was to investigate the effect and the underlying mechanism of KLK6 on stem cell-like properties and metabolism in gastric carcinoma cells. The HGC-27 cell line was transfected with KLK6 overexpression (OV-KLK6) and interference (short hairpin-KLK6) vectors, then the transfection efficiency was confirmed using western blot analysis and reverse transcription-quantitative PCR. The percentage of CD133+ and CD44+ cells was detected using flow cytometry, while the protein expression levels of the stem-associated genes, Nanog, Oct-4, SOX2 and Notch1, the metabolic markers, hexokinase (HK)1, HK2, GLUT1, and the proteins within the PI3K signaling pathway, phosphorylated (p)-PI3K, p-AKT and p-mTOR, were determined using western blot analysis. Biochemical kits were used to measure ATP production, lactic acid content and glucose uptake. A tumorigenicity assay was performed with nude mice to detect gastric tumor volume, and the protein expression level of Oct-4, Nanog, HK1, HK2 and GLUT1, and the mRNA expression level of KLK6 was also determined in gastric tumor tissues of mice. Compared with that in the control group, KLK6 protein and mRNA expression levels were significantly decreased in the four sh-RNA groups (P<0.05). Among them, sh-RNA-3 induced the lowest KLK6 expression and was used to silence KLK6 in subsequent experiments. Compared with that in the control and negative control groups, the percentage of CD133+ and CD44+ cells, the protein expression level of Oct-4, Nanog, HK1, HK2, GLUT1, p-PI3K, p-AKT and p-mTOR, and ATP content, lactic acid production, glucose uptake and gastric tumor volume were significantly decreased by sh-KLK6 (P<0.05), whereas KLK6 overexpression induced the opposite effect (P<0.05). In conclusion, KLK6 modulated stemness properties and cell metabolic profile in gastric carcinoma cells and the mechanism may be associated with the PI3K/AKT/mTOR signaling pathway.
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Affiliation(s)
- Dong Zhou
- Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei Medical College, Xiangyang, Hubei 441000, P.R. China
| | - Yanping He
- Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei Medical College, Xiangyang, Hubei 441000, P.R. China
| | - Hengping Li
- Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei Medical College, Xiangyang, Hubei 441000, P.R. China
| | - Weidong Huang
- Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei Medical College, Xiangyang, Hubei 441000, P.R. China
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Keyvani-Ghamsari S, Khorsandi K, Rasul A, Zaman MK. Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance. Clin Epigenetics 2021; 13:120. [PMID: 34051847 PMCID: PMC8164819 DOI: 10.1186/s13148-021-01107-4] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 05/19/2021] [Indexed: 12/13/2022] Open
Abstract
At present, after extensive studies in the field of cancer, cancer stem cells (CSCs) have been proposed as a major factor in tumor initiation, progression, metastasis, and recurrence. CSCs are a subpopulation of bulk tumors, with stem cell-like properties and tumorigenic capabilities, having the abilities of self-renewal and differentiation, thereby being able to generate heterogeneous lineages of cancer cells and lead to resistance toward anti-tumor treatments. Highly resistant to conventional chemo- and radiotherapy, CSCs have heterogeneity and can migrate to different organs and metastasize. Recent studies have demonstrated that the population of CSCs and the progression of cancer are increased by the deregulation of different epigenetic pathways having effects on gene expression patterns and key pathways connected with cell proliferation and survival. Further, epigenetic modifications (DNA methylation, histone modifications, and RNA methylations) have been revealed to be key drivers in the formation and maintenance of CSCs. Hence, identifying CSCs and targeting epigenetic pathways therein can offer new insights into the treatment of cancer. In the present review, recent studies are addressed in terms of the characteristics of CSCs, the resistance thereof, and the factors influencing the development thereof, with an emphasis on different types of epigenetic changes in genes and main signaling pathways involved therein. Finally, targeted therapy for CSCs by epigenetic drugs is referred to, which is a new approach in overcoming resistance and recurrence of cancer.
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Affiliation(s)
| | - Khatereh Khorsandi
- Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran.
| | - Azhar Rasul
- Department of Zoology, Government College University Faisalabad, Faisalabad, 38000, Pakistan
| | - Muhammad Khatir Zaman
- Department of Biotechnology, Abdul Wali Khan University Mardan (AWKUM), Mardan, 23200, Pakistan
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Abstract
Defined by its potential for self-renewal, differentiation and tumorigenicity, cancer stem cells (CSCs) are considered responsible for drug resistance and relapse. To understand the behavior of CSC, the effects of the microenvironment in each tissue are a matter of great concerns for scientists in cancer biology. However, there are many complicated obstacles in the mimicking the microenvironment of CSCs even with current advanced technology. In this context, novel biomaterials have widely been assessed as in vitro platforms for their ability to mimic cancer microenvironment. These efforts should be successful to identify and characterize various CSCs specific in each type of cancer. Therefore, extracellular matrix scaffolds made of biomaterial will modulate the interactions and facilitate the investigation of CSC associated with biological phenomena simplifying the complexity of the microenvironment. In this review, we summarize latest advances in biomaterial scaffolds, which are exploited to mimic CSC microenvironment, and their chemical and biological requirements with discussion. The discussion includes the possible effects on both cells in tumors and microenvironment to propose what the critical factors are in controlling the CSC microenvironment focusing the future investigation. Our insights on their availability in drug screening will also follow the discussion.
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El-Khoury F, Bignon J, Martin JR. jouvence, a new human snoRNA involved in the control of cell proliferation. BMC Genomics 2020; 21:817. [PMID: 33225905 PMCID: PMC7682050 DOI: 10.1186/s12864-020-07197-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 10/27/2020] [Indexed: 12/15/2022] Open
Abstract
Background Small nucleolar RNAs (snoRNAs) are non-coding RNAs that are conserved from archaebacteria to mammals. They are associated in the nucleolus, with proteins to form small nucleolar ribonucleoprotein (snoRNPs). They modify ribosomal RNAs, for example, the H/ACA box that converts uridine to pseudouridine. In humans, various pathologies have been associated with snoRNAs, and several snoRNAs have been reported to participate in many cancer processes. Recently, a new H/ACA box snoRNA named jouvence has been identified in Drosophila and has been shown to be involved in lifespan determination in relation to gut homeostasis. Because snoRNAs are conserved through evolution, both structurally and functionally, a jouvence orthologue has been identified in humans. RT-PCR has revealed that jouvence is expressed, suggesting that it might be functional. These results suggest the hypothesis that jouvence may display similar functions, including increasing the healthy lifespan in humans. Results Here, we report the characterization of the human snoRNA jouvence, which has not yet been annotated in the genome. We show that its overexpression significantly stimulates cell proliferation, both in various stable cancerous cell lines as well as in primary cells. By contrast, its knockdown by siRNA leads to the opposite phenotype, a rapid decrease in cell proliferation. Transcriptomic analysis (RNA-Seq) revealed that the overexpression of jouvence leads to a dedifferentiation signature of the cells. Conversely, the knockdown of jouvence led to a striking decrease in the expression levels of genes involved in ribosome biogenesis and the spliceosome. Conclusion The overexpression of a single and short non-coding RNA of 159 nucleotides, the snoRNA-jouvence, seems to be sufficient to reorient cells toward stemness, while its depletion blocks cell proliferation. In this context, we speculate that the overexpression of jouvence, which appears to be a non-canonical H/ACA snoRNA, could represent a new tool to fight against the deleterious effects of aging, while inversely, its knockdown by siRNA could represent a new approach in cancer therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12864-020-07197-3.
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Affiliation(s)
- Flaria El-Khoury
- Equipe: Imagerie Cérébrale Fonctionnelle et Comportements (ICFC), Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR-9197, CNRS/Université Paris-Saclay, 1 Avenue de la Terrasse (Bat. 32/33), 91198, Gif-sur-Yvette, France
| | - Jérôme Bignon
- Institut de Chimie des Substances Naturelles, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France
| | - Jean-René Martin
- Equipe: Imagerie Cérébrale Fonctionnelle et Comportements (ICFC), Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR-9197, CNRS/Université Paris-Saclay, 1 Avenue de la Terrasse (Bat. 32/33), 91198, Gif-sur-Yvette, France.
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13
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Sun Z, Wang L, Zhou Y, Dong L, Ma W, Lv L, Zhang J, Wang X. Glioblastoma Stem Cell-Derived Exosomes Enhance Stemness and Tumorigenicity of Glioma Cells by Transferring Notch1 Protein. Cell Mol Neurobiol 2020; 40:767-784. [PMID: 31853695 PMCID: PMC11448788 DOI: 10.1007/s10571-019-00771-8] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 12/03/2019] [Indexed: 02/05/2023]
Abstract
Exosomes contain plenty of bioactive information, playing an important role in intercellular communication by transfer their bioactive molecular contents to recipient cells. Glioblastoma stem cells (GSCs) and non-GSC glioma cells coexist in GBM microenvironment; GSC-released exosomes contain intracellular signaling molecules, which may affect the biological phenotypes of recipient cells. However, whether GSC exosomes could affect the biological phenotype of non-GSC glioma cells has not yet been defined. To explore whether GSC exosomes could reprogramme non-GSC glioma cells into GSCs and its possible mechanism involved, non-GSC glioma cells were treated with GSCs released exosomes; the potential mechanisms of action were studied with RNA interference, Notch inhibitors and Western blot analysis. The proliferation, neurosphere formation, invasive capacities, and tumorigenicity of non-GSC glioma cells were increased significantly after GSC exosome treatment; Notch1 signaling pathway was activated in GSCs; Notch1 protein was highly enriched in GSC exosomes; Notch1 signaling pathway and stemness-related protein expressions were increased in GSC exosome treated non-GSC glioma cells and these cell generated tumor tissues; Notch1 protein expression in GSCs and their exosomes, and the neurosphere formation of GSCs were decreased by Notch1 RNA interference; Notch1 signaling pathway protein and stemness protein expressions were decreased in GSC exosome treated non-GSC glioma cells by Notch1 RNA interference and Notch inhibitors. The findings in this study indicated that GSC exosomes act as information carriers, mediated non-GSC glioma cell dedifferentiation into GSCs by delivering Notch1 protein through Notch1 signaling activation, and enhanced stemness and tumorigenicity of non-GSC glioma cells.
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Affiliation(s)
- Zhen Sun
- Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, No. 1 Keyuan Road 4, Gaopeng Avenu, Hi-tech Zone, Chengdu, 610041, China
| | - Li Wang
- Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, No. 1 Keyuan Road 4, Gaopeng Avenu, Hi-tech Zone, Chengdu, 610041, China
| | - Yueling Zhou
- Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, No. 1 Keyuan Road 4, Gaopeng Avenu, Hi-tech Zone, Chengdu, 610041, China
| | - Lihua Dong
- Human Anatomy Department, School of Preclinical and Forensic Medcine, Sichuan University, Chengdu, 610041, China
| | - Weichao Ma
- Neurosurgery Department, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Liang Lv
- Neurosurgery Department, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jie Zhang
- Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, No. 1 Keyuan Road 4, Gaopeng Avenu, Hi-tech Zone, Chengdu, 610041, China
| | - Xiujie Wang
- Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, No. 1 Keyuan Road 4, Gaopeng Avenu, Hi-tech Zone, Chengdu, 610041, China.
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14
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Ozturk S, Gorgun C, Gokalp S, Vatansever S, Sendemir A. Development and characterization of cancer stem cell-based tumoroids as an osteosarcoma model. Biotechnol Bioeng 2020; 117:2527-2539. [PMID: 32391924 DOI: 10.1002/bit.27381] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 03/04/2020] [Accepted: 05/07/2020] [Indexed: 12/24/2022]
Abstract
Three-dimensional (3D) cancer tumor models are becoming vital approaches for high-throughput drug screening, drug targeting, development of novel theranostic systems, and personalized medicine. Yet, it is becoming more evident that the tumor progression and metastasis is fueled by a subpopulation of stem-like cells within the tumor that are also called cancer stem cells (CSCs). This study aimed to develop a tumoroid model using CSCs. For this purpose CD133+ cells were isolated from SaOS-2 osteosarcoma cell line with magnetic-activated cell sorting. To evaluate tumoroid formation ability, the cells were incubated in different cell numbers in agar gels produced by 3D Petri Dish® method. Subsequently, CD133+ cells and CD133- cells were co-cultured to investigate CD133+ cell localization in tumoroids. The characterization of tumoroids was performed using Live&Dead staining, immunohistochemistry, and quantitative polymerase chain reaction analysis. The results showed that, CD133+ , CD133- and SaOS-2 cells were all able to form 3D tumoroids regardless of the initial cell number, but, while 72 hr were needed for CD133+ cells to self-assemble, 24 hr were enough for CD133- and SaOS-2 cells. CD133+ cells were located within tumoroids randomly with high cell viability. Finally, when compared to two-dimensional (2D) cultures, there were 5.88, 4.14, 6.95, and 1.68-fold higher messenger RNA expressions for Sox2, OCT3/4, Nanog, and Nestin, respectively, in CD133+ cells that were cultured within 3D tumoroids, showing longer maintenance of stem cell phenotype in 3D, that can allow more relevant screening and targeting efficiency in pharmaceutical testing. It was concluded that CSC-based tumoroids are propitious as 3D tumor models to fill the gap between conventional 2D in vitro culture and in vivo animal experiments for cancer research.
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Affiliation(s)
- Sukru Ozturk
- Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.,Bioengineering Division, Institute for Graduate Studies in Science and Engineering, Hacettepe University, Ankara, Turkey.,Department of Biomedical Technologies, Graduate School of Natural and Applied Sciences, Ege University, Izmir, Turkey
| | - Cansu Gorgun
- Department of Biomedical Technologies, Graduate School of Natural and Applied Sciences, Ege University, Izmir, Turkey.,Department of Experimental Medicine, University of Genova, Genova, Italy
| | - Sevtap Gokalp
- Department of Histology and Embryology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.,Department of Histology and Embryology, Faculty of Medicine, Maltepe University, Istanbul, Turkey
| | - Seda Vatansever
- Department of Histology and Embryology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.,Research Center of Experimental Health Sciences (DESAM), Near East University, Mersin, Turkey
| | - Aylin Sendemir
- Department of Biomedical Technologies, Graduate School of Natural and Applied Sciences, Ege University, Izmir, Turkey.,Department of Bioengineering, Faculty of Engineering, Ege University, Izmir, Turkey
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15
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Abstract
Cancer stem cells (CSCs) are a small subpopulation of cells associated with cancer initiation, progression, metastasis, therapy resistant, and recurrence. In esophageal squamous cell carcinoma (ESCC), several cell surface and intracellular markers, for example, CD44, ALDH, Pygo2, MAML1, Twist1, Musashi1, side population (SP), CD271, and CD90, have been proposed to identify CSCs. In addition, stem cell markers such as ALDH1, HIWI, Oct3/4, ABCG2, SOX2, SALL4, BMI-1, NANOG, CD133, and podoplanin were associated with pathological stages of cancer, cancer recurrence, prognosis, and therapy resistance of patients with ESCC. Identification and isolation of CSCs could play an important part of improved cancer management regime in ESCC. Furthermore, CSCs may be used as the predictive tool for chemoradiotherapy response in ESCC. Different methods such as in vitro functional assays, cell sorting using various intracellular, and cell surface markers and xenotransplantation techniques are frequently used for the identification and isolation of CSCs in different cancers, including ESCC. However, none of these methods solely can guarantee complete isolation of CSC population. Therefore, a combination of methods is used for reliable detection and isolation of CSCs. Herein, we describe the identification and isolation of CSCs from ESCC cells by cell sorting after Hoechst 33342 staining followed by in vitro functional assays and in vivo mouse xenotransplantation techniques.
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16
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Abstract
Cancer-initiating cells (CIC) are the driving force in tumor progression. There is strong evidence that CIC fulfill this task via exosomes (TEX), which modulate and reprogram stroma, nontransformed cells, and non-CIC. Characterization of CIC, besides others, builds on expression of CIC markers, many of which are known as metastasis-associated molecules. We here discuss that the linkage between CIC/CIC-TEX and metastasis-associated molecules is not fortuitously, but relies on the contribution of these markers to TEX biogenesis including loading and TEX target interactions. In addition, CIC markers contribute to TEX binding- and uptake-promoted activation of signaling cascades, transcription initiation, and translational control. Our point of view will be outlined for pancreas and colon CIC highly expressing CD44v6, Tspan8, EPCAM, claudin7, and LGR5, which distinctly but coordinately contribute to tumor progression. Despite overwhelming progress in unraveling the metastatic cascade and the multiple tasks taken over by CIC-TEX, there remains a considerable gap in linking CIC biomarkers, TEX, and TEX-initiated target modulation with metastasis. We will try to outline possible bridges, which could allow depicting pathways for new and expectedly powerful therapeutic interference with tumor progression.
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Affiliation(s)
- Zhe Wang
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
| | - Margot Zöller
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
- Pancreas Section, University Hospital of Surgery, Heidelberg, Germany.
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17
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Abbasian M, Mousavi E, Arab-Bafrani Z, Sahebkar A. The most reliable surface marker for the identification of colorectal cancer stem-like cells: A systematic review and meta-analysis. J Cell Physiol 2019; 234:8192-8202. [PMID: 30317669 DOI: 10.1002/jcp.27619] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Accepted: 09/24/2018] [Indexed: 12/17/2022]
Abstract
Several surface markers have been proposed for the identification and characterization of colorectal cancer stem-like cells (CR-CSLCs). However, their reliability in CR-CSLCs identification remains controversial. This study evaluated the correlation between all candidate surface marker's expression and CSLCs properties (tumorigenicity) through monitoring in vivo tumor incidence and final tumor volume. PubMed, Web of Science, and Scopus databases were systematically searched until November 2017. A total of 27 studies were found that met the inclusion criteria for cluster of differentiation 133 (CD133) and CD44 markers. Results indicated that either CD133 or CD44 positive cells caused about twofold increase in tumor volume compared with the negative cells (p < 0.05). In two groups of cells derived from primary tumors and cell lines, CD133 + cells had 25 and 1.45 times higher tumor incidence potential than CD133 - cells, respectively ( p < 0.05). Also, cohort evaluation showed that CD133 overexpression at protein level is a marker of poor overall survival in colorectal cancer (CRC) patients. While CD44 + cells displayed twofold tumorigenicity compared with the negative cells ( p < 0.05), combination of CD44 and CD133 showed about sevenfold tumorigenicity potential ( p < 0.05). In conclusion, the present meta-analysis suggests that CD133 is a robust biomarker to identify primary tumor CSLCs and can be proposed as a prognostic marker of CRC patient whereas it should be used with caution in cell lines. It seems to be more reliable to use CD133 in combination with CD44 as target biomarkers for the isolation of CR-CSLCs in both cell line and primary tumor cells populations.
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Affiliation(s)
- Mahdi Abbasian
- Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
- Department of Biotechnology, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
| | - Elham Mousavi
- Department of Medical Microbiology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Zahra Arab-Bafrani
- Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
- Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
- Stem Cell Research Center, Golestan University of Medical Science, Gorgan, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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18
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Abstract
Cancer is one of the most serious diseases all over the world, and the cancer stem cell (CSC) model accounts for tumor initiation, metastasis, drug resistance, and relapse. The CSCs within tumor bulk have the capacity to self-renew, differentiate, and give rise to a new tumor. The self-renewal of CSCs is precisely regulated by various modulators, including Wnt/β-catenin signaling, Notch signaling, Hedgehog signaling, transcription factors, chromatin remodeling complexes, and non-coding RNAs. CSCs reside in their niches that are also involved in the self-renewal maintenance of CSCs and protection of CSCs from chemotherapy, radiotherapy, and even endogenous damages. Moreover, CSCs can also remodel their niches to initiate tumorigenesis. The mutual interactions between CSCs and their niches play a critical role in the regulation of CSC self-renewal and tumorigenesis as well. Many surface markers of CSCs have been identified, and these markers become first choices for CSC targeting. Due to heterogeneity and plasticity, targeting CSCs is still a big challenge for tumor elimination. In this review, we summarize recent progresses on the biological features of CSCs and targeting strategies against CSCs.
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Affiliation(s)
- Pingping Zhu
- 1CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China
| | - Zusen Fan
- 1CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China.,2University of Chinese Academy of Sciences, Beijing, 100049 China
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19
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Prabavathy D, Swarnalatha Y, Ramadoss N. Lung cancer stem cells-origin, characteristics and therapy. Stem Cell Investig 2018; 5:6. [PMID: 29682513 DOI: 10.21037/sci.2018.02.01] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 01/16/2018] [Indexed: 12/24/2022]
Abstract
Cancer stem cells (CSCs) have gained an increasing attention recently in cancer research. CSCs have ability to generate new tumor through their stem cell properties, essentially self-renewal potential and differentiation into multiple cell lineages. Extensive evidences report that CSCs are resistant to many conventional therapies and mediate tumor recurrence. CSCs of lung cancer are well recognized by their specific markers such as CD133, CD44, ABCG2 and ALDH1A1 together with the CSC characteristics including spheroid and colony formation. Targeting these surface proteins with blocking antibodies and inhibition of ABC transporters and aldehyde dehydrogenase (ALDH) enzymes with small molecules may prove useful in inhibiting tumor progression. The Hh, Notch and Wnt pathways are key signaling cascades that govern cell fate during development and have been shown to be involved in CSCs in various solid tumors. Therapeutic approaches also target these signaling pathways in repressing the tumor progression. This review will focus on stem cell origins, role of signaling pathways, stem cell markers and therapeutic approaches specific to lung cancer.
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Affiliation(s)
- D Prabavathy
- Department of Biotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science & Technology (Deemed to be University), Rajiv Gandhi Salai, Chennai-119, Tamilnadu, India
| | - Y Swarnalatha
- Department of Biotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science & Technology (Deemed to be University), Rajiv Gandhi Salai, Chennai-119, Tamilnadu, India
| | - Niveditha Ramadoss
- Department of Biology, California State University Northridge, Northridge, CA, USA
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20
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Abstract
Single-cell analysis has become an established method to study cell heterogeneity and for rare cell characterization. Despite the high cost and technical constraints, applications are increasing every year in all fields of biology. Following the trend, there is a tremendous development of tools for single-cell analysis, especially in the RNA sequencing field. Every improvement increases sensitivity and throughput. Collecting a large amount of data also stimulates the development of new approaches for bioinformatic analysis and interpretation. However, the essential requirement for any analysis is the collection of single cells of high quality. The single-cell isolation must be fast, effective, and gentle to maintain the native expression profiles. Classical methods for single-cell isolation are micromanipulation, microdissection, and fluorescence-activated cell sorting (FACS). In the last decade several new and highly efficient approaches have been developed, which not just supplement but may fully replace the traditional ones. These new techniques are based on microfluidic chips, droplets, micro-well plates, and automatic collection of cells using capillaries, magnets, an electric field, or a punching probe. In this review we summarize the current methods and developments in this field. We discuss the advantages of the different commercially available platforms and their applicability, and also provide remarks on future developments.
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