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Meng Y, Tuersuntuoheti A, Jiang S, Xie J, Yue Z, Xu D, Geng X, Lian X, Xie L, Sung LA, Wang X, Zhou J, Yao W. Tropomodulin1 regulates the biomechanical changes in macrophages induced by matrix stiffness. MECHANOBIOLOGY IN MEDICINE 2025; 3:100117. [PMID: 40395777 PMCID: PMC12067908 DOI: 10.1016/j.mbm.2025.100117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 01/14/2025] [Accepted: 02/13/2025] [Indexed: 03/15/2025]
Abstract
The monocyte/macrophage infiltration plays critical roles in the development of atherosclerosis. Arterial stiffness is a cholesterol-independent risk factor for cardiovascular events. The regulation of arterial stiffness on biomechanics of macrophages and its underlying mechanism remains unclear. We prepared polyacrylamide gels with low and high stiffness that corresponded to healthy and diseased blood vessels, respectively. We found that macrophages cultured on stiff matrix had increased rigidity and migration ability compared to those on soft matrix. An actin capping protein, tropomodulin1 (Tmod1) was upregulated in macrophages by stiff matrix and in arteries with high stiffness. Further analyses showed that deficiency of Tmod1 in macrophages completely or partially prevented the changes in actin polymerization, cell adhesion and cell spreading induced by stiff matrix. Overexpression of Tmod1 in macrophages enhanced actin polymerization, cell adhesion and spreading on stiff matrix. Tmod1 was involved in the regulation of vinculin expression and formation of focal adhesion in macrophages on stiff matrix. Finally, the deficiency of Tmod1 in macrophages retarded the formation of atherosclerotic plaques in blood vessels with high matrix stiffness. The results suggest that Tmod1 was a key regulator in macrophage rigidity and migration on stiff substrate. The present work will help us to understand the biomechanical mechanisms for the development of atherosclerosis.
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Affiliation(s)
- Yajun Meng
- Hemorheology Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
- Chengde Medical College, Chengde, Hebei Province, 067000, China
| | - Amannisa Tuersuntuoheti
- Hemorheology Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Siyu Jiang
- Hemorheology Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
- Chengde Medical College, Chengde, Hebei Province, 067000, China
| | - Jiayi Xie
- Department of Automatic, Tsinghua University, Beijing 100084, China
| | - Zejun Yue
- Hemorheology Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Dingwen Xu
- Department of Clinic, School of Medical Science, Yangzhou Polytechnic College, Yangzhou, Jiangsu Province, 225127, China
| | - Xueyu Geng
- Hemorheology Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Xiang Lian
- Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Lide Xie
- Chengde Medical College, Chengde, Hebei Province, 067000, China
| | - Lanping Amy Sung
- Department of Bioengineering, University of California, La Jolla, San Diego, 92093, CA, USA
| | - Xifu Wang
- Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Jing Zhou
- Hemorheology Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Weijuan Yao
- Hemorheology Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University Health Center, Beijing, 100191, China
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Li Y, Sun Y, Yu K, Li Z, Miao H, Xiao W. Keratin: A potential driver of tumor metastasis. Int J Biol Macromol 2025; 307:141752. [PMID: 40049479 DOI: 10.1016/j.ijbiomac.2025.141752] [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: 10/08/2024] [Revised: 02/26/2025] [Accepted: 03/03/2025] [Indexed: 03/19/2025]
Abstract
Keratins, as essential components of intermediate filaments in epithelial cells, play a crucial role in maintaining cell structure and function. In various malignant epithelial tumors, abnormal keratin expression is frequently observed and serves not only as a diagnostic marker but also closely correlates with tumor progression. Extensive research has demonstrated that keratins are pivotal in multiple stages of tumor metastasis, including responding to mechanical forces, evading the immune system, reprogramming metabolism, promoting angiogenesis, and resisting apoptosis. Here we emphasize that keratins significantly enhance the migratory and invasive capabilities of tumor cells, making them critical drivers of tumor metastasis. These findings highlight the importance of targeting keratins as a strategic approach to combat tumor metastasis, thereby advancing our understanding of their role in cancer progression and offering new therapeutic opportunities.
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Affiliation(s)
- Yuening Li
- Army Medical University, Chongqing, China
| | - Yiming Sun
- Department of General Surgery, the Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Kun Yu
- Department of General Surgery, the Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Zhixi Li
- Department of General Surgery, the Second Affiliated Hospital of Army Medical University, Chongqing, China.
| | - Hongming Miao
- Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University, Chongqing 400038, China; Jinfeng Laboratory, Chongqing, China.
| | - Weidong Xiao
- Department of General Surgery, the Second Affiliated Hospital of Army Medical University, Chongqing, China.
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Lou K, Cheng X. Prognostic value of the neutrophil‑to‑lymphocyte ratio in renal cell carcinoma: A systematic review and meta‑analysis. Oncol Lett 2025; 29:231. [PMID: 40114748 PMCID: PMC11925002 DOI: 10.3892/ol.2025.14977] [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: 11/01/2024] [Accepted: 02/11/2025] [Indexed: 03/22/2025] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) not only indicates the inflammatory response within the tumor microenvironment but may also correlate with tumor biological behavior (such as aggressiveness). The present study aimed to systematically review and conduct a meta-analysis on the impact of the NLR on the prognosis of patients with renal cell carcinoma (RCC). To this aim, a comprehensive search of multiple relevant databases, including PubMed, Embase and the Cochrane Library, was conducted to identify literature related to NLR and RCC prognosis. Following rigorous literature screening and quality assessment, a systematic quantitative analysis was ultimately performed on several studies that met the inclusion criteria. The results indicated a significant association between elevated NLR levels and poor prognosis in patients with RCC, suggesting that high NLR levels may serve as an independent predictor of unfavorable outcomes. Therefore, the present study provides important evidence for clinical decision-making, further demonstrating that NLR can serve as an independent prognostic indicator for patients with RCC, aiding healthcare professionals in making more precise judgments in patient management and treatment strategy formulation.
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Affiliation(s)
- Kecheng Lou
- Department of Urology, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Xin Cheng
- Department of Urology, Ganzhou Cancer Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
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Luo Z, Chen S, Chen P, Xiong K, Cao C. Association of dietary inflammatory index, composite dietary antioxidant index and risk of death among adult cancer survivors: findings from the National Health and Nutrition Examination Survey 2001-2018. Front Immunol 2025; 16:1556828. [PMID: 40260237 PMCID: PMC12009815 DOI: 10.3389/fimmu.2025.1556828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 03/19/2025] [Indexed: 04/23/2025] Open
Abstract
Background The development and progression of cancer can be impacted by the nutrients and components contained in the diet. This research seeks to explore the relationship between the antioxidant and pro-inflammatory properties of diet and the risk of all-cause mortality among cancer survivors. Methods Adults aged 20 and above who had been diagnosed with cancer and participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018 were selected for this study. Their survival status was verified using death certificate information from the National Death Index. The study employed two established measures, the Composite Dietary Antioxidant Index (CDAI) and the Dietary Inflammatory Index (DII), to evaluate the antioxidant and inflammatory properties of participants' diets. A non-linear association between these two dietary indices and mortality was examined respectively using restricted cubic spline (RCS) regression. To quantify the relationship between the indices and mortality risk, multivariable Cox proportional hazards models were employed, generating hazard ratios and corresponding 95% confidence intervals. Furthermore, the study also explored the connection between the CDAI and DII. Results In this study, a total of 3,507 cancer survivors, representing an estimated 20,016,255 cancer survivors in the US, were included in the baseline analysis. The results showed that patients with lower DII or higher CDAI values had better survival rates. RCS regression revealed that both indicators showed linear relationships with all-cause mortality in the crude and adjusted models. It was consistently noted higher CDAI or lower DII was related to a reduced risk of all-cause mortality in cancer survivors in the Cox regression. Moreover, the subgroup analysis demonstrated that these associations hold true across various subgroups, lending credibility to the overall findings of the study. At last, an inverse correlation was observed between CDAI and DII in the diets of cancer survivors. Conclusion The research suggests that adopting a diet that low in pro-inflammatory foods and high in antioxidants may lower the all-cause mortality in cancer survivors. However, further prospective cohort studies are necessary to confirm these findings.
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Affiliation(s)
| | | | | | | | - Chao Cao
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
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Campanile R, Helenius J, Scielzo C, Scarfò L, Salerno D, Bossi M, Falappi M, Saponara A, Müller DJ, Mantegazza F, Cassina V. Production of AFM wedged cantilevers for stress-relaxation experiments: Uniaxial loading of soft, spherical cells. Methods 2025; 236:1-9. [PMID: 39971021 DOI: 10.1016/j.ymeth.2025.02.004] [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: 11/13/2024] [Revised: 01/30/2025] [Accepted: 02/13/2025] [Indexed: 02/21/2025] Open
Abstract
The fabrication of wedge-shaped cantilevers for Atomic Force Microscopy (AFM) remains a critical yet challenging task, particularly when precision and efficiency are required. In this study, we present a streamlined protocol for producing these wedges using NOA63 UV-curing polymer, which simplifies the process and eliminates the need for dedicated equipment. Our method reduces preparation time while maintaining the mechanical properties of the cantilevers, in line with the manufacturer's specifications. We demonstrate the effectiveness of our wedged cantilevers in stress-relaxation experiments performed by means of AFM and confocal microscopy on primary Chronic Lymphocytic Leukemia cells and the MEC1 cell line. These experiments highlight the effectiveness of using modified cantilevers to consistently apply precise uniaxial loading to soft, spherical cells. This technique offers a marked improvement in fabrication speed and operational ease compared to traditional methods, without compromising the accuracy or performance of the measurements. This protocol is not only time-saving, but also adaptable for use in a wide range of biological applications, making it a valuable tool for AFM-based research in cellular mechanics.
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Affiliation(s)
- Riccardo Campanile
- School of Medicine and Surgery, BioNanoMedicine Center NANOMIB, Università di Milano-Bicocca, Vedano al Lambro, Italy
| | - Jonne Helenius
- Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland
| | - Cristina Scielzo
- Division of Experimental Oncology, Malignant B cells biology and 3D modelling Unit, IRCCS Ospedale San Raffaele Milano, Italy
| | - Lydia Scarfò
- School of Medicine, Università Vita-Salute San Raffaele, Milano, Italy; Division of Experimental oncology, B-cell neoplasia Unit and Strategic Research Program on CLL, IRCCS Ospedale San Raffaele, Milano, Italy
| | - Domenico Salerno
- School of Medicine and Surgery, BioNanoMedicine Center NANOMIB, Università di Milano-Bicocca, Vedano al Lambro, Italy
| | - Mario Bossi
- School of Medicine and Surgery, BioNanoMedicine Center NANOMIB, Università di Milano-Bicocca, Vedano al Lambro, Italy
| | - Marta Falappi
- School of Medicine and Surgery, BioNanoMedicine Center NANOMIB, Università di Milano-Bicocca, Vedano al Lambro, Italy
| | - Alessia Saponara
- School of Medicine and Surgery, BioNanoMedicine Center NANOMIB, Università di Milano-Bicocca, Vedano al Lambro, Italy
| | - Daniel J Müller
- Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland
| | - Francesco Mantegazza
- School of Medicine and Surgery, BioNanoMedicine Center NANOMIB, Università di Milano-Bicocca, Vedano al Lambro, Italy
| | - Valeria Cassina
- School of Medicine and Surgery, BioNanoMedicine Center NANOMIB, Università di Milano-Bicocca, Vedano al Lambro, Italy.
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Chaithanya KVS, Rozman J, Košmrlj A, Sknepnek R. Cell-Level Modelling of Homeostasis in Confined Epithelial Monolayers. JOURNAL OF ELASTICITY 2025; 157:29. [PMID: 40013236 PMCID: PMC11850549 DOI: 10.1007/s10659-025-10120-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 02/10/2025] [Indexed: 02/28/2025]
Abstract
Tissue homeostasis, the biological process of maintaining a steady state in tissue via control of cell proliferation and death, is essential for the development, growth, maintenance, and proper function of living organisms. Disruptions to this process can lead to serious diseases and even death. In this study, we use the vertex model for the cell-level description of tissue mechanics to investigate the impact of the tissue environment and local mechanical properties of cells on homeostasis in confined epithelial tissues. We find a dynamic steady state, where the balance between cell divisions and removals sustains homeostasis, and characterise the homeostatic state in terms of cell count, tissue area, homeostatic pressure, and the cells' neighbour count distribution. This work, therefore, sheds light on the mechanisms underlying tissue homeostasis and highlights the importance of mechanics in its control.
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Affiliation(s)
- KVS Chaithanya
- School of Life Sciences, University of Dundee, Dundee, DD1 5EH UK
- School of Science and Engineering, University of Dundee, Dundee, DD1 4HN UK
| | - Jan Rozman
- Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Oxford, OX1 3PU UK
| | - Andrej Košmrlj
- Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 USA
- Princeton Materials Institute, Princeton University, Princeton, NJ 08544 USA
| | - Rastko Sknepnek
- School of Life Sciences, University of Dundee, Dundee, DD1 5EH UK
- School of Science and Engineering, University of Dundee, Dundee, DD1 4HN UK
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Zhao W, Li D, Liu X, Gao W, Chang Z, Chen P, Sun X, Zhao Y, Liu H, Wu D, Wang S, Zhang Y, Jiao H, Wan X, Dong G. Nutritional and inflammatory status dynamics reflect preoperative treatment response and predict prognosis in locally advanced rectal cancer: A retrospective multi-institutional analysis. Surgery 2025; 178:108965. [PMID: 39667110 DOI: 10.1016/j.surg.2024.108965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/28/2024] [Accepted: 11/12/2024] [Indexed: 12/14/2024]
Abstract
BACKGROUND Systemic inflammation, as an important host property, is the most representative tumor-host interactions in cancer, and the development of malignant neoplasms may contribute to impairment on nutritional status. This study aimed to investigate the potential ability of nutritional and inflammatory index in predicting neoadjuvant chemoradiotherapy efficacy and prognosis in locally advanced rectal cancer (LARC). METHODS This study was conducted using multi-institutional data. A total of 507 patients (262 in the training and 245 in the validation cohort) with stage IIA-IIIC LARC fit for neoadjuvant chemoradiotherapy were recruited from 2012 to 2014 were included in this study. Advanced lung cancer inflammation index (ALI) reflected nutritional and inflammatory status. The ALI was calculated as body mass index (BMI) × albumin × neutrophil/lymphocyte. Logistic regression model was used to identify predictive factors for preoperative treatment response. Cox multivariate regression models were used to analyze the factors affecting disease-free survival (DFS) and overall survival (OS). RESULTS In the training cohort, patients with high pretreatment ALI were observed to be associated with young patients, never smoked, relatively high BMI, and early-stage pathologic TNM staging. The receiver operating characteristic curve indicated that pretreatment ALI and its changing was the single most important factor determining outcomes than other inflammatory indicators. The 10-year DFS and OS rates of the whole group were 63.6% and 74.1% respectively. Patients with low pretreatment ALI and ALI change had significantly poorer 10-year DFS (P < .001 and P = .001) and 10-year OS (P = .002 and P = .025) rates than those with high ALI and ALI change. Similar findings were observed in the validation cohort. Multivariate analysis revealed that pretreatment ALI (P = .047 and P = .006) and ALI change (P = .027 and P = .041) were identified as independent prognostic factors for DFS. Meanwhile, high pretreatment ALI (P = .020 and P = .010), high systemic immune-inflammation index (SII) change (P = .040 and P = .012) and clinical stage T2-T3 were independent protective factors for OS. Furthermore, multivariate logistic regression analyses revealed that pretreatment ALI, ALI change, and SII change could independently predict efficacy of neoadjuvant chemoradiotherapy. CONCLUSION Our results suggest that as a feasible indicator of nutritional and inflammatory status, the ALI shows better efficiency than other inflammatory indicators in predicting efficacy of neoadjuvant chemoradiotherapy and prognosis.
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Affiliation(s)
- Wen Zhao
- School of Medicine, Nankai University, Tianjin, China; Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Dingchang Li
- Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Xianqiang Liu
- Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Wenxing Gao
- Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Zhengyao Chang
- Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Peng Chen
- Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xu Sun
- School of Medicine, Nankai University, Tianjin, China; Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yingjie Zhao
- Department of General Surgery, the Eighth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hao Liu
- School of Medicine, Nankai University, Tianjin, China; Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Di Wu
- Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Sizhe Wang
- School of Medicine, Nankai University, Tianjin, China; Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yinqi Zhang
- School of Medicine, Nankai University, Tianjin, China; Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hanqing Jiao
- Department of General Surgery, the Affiliated Cancer Hospital of Zhengzhou University, China
| | - Xiangbin Wan
- Department of General Surgery, the Affiliated Cancer Hospital of Zhengzhou University, China.
| | - Guanglong Dong
- School of Medicine, Nankai University, Tianjin, China; Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China.
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Kim H, Kim KE, Madan E, Martin P, Gogna R, Rhee HW, Won KJ. Unveiling contact-mediated cellular crosstalk. Trends Genet 2024; 40:868-879. [PMID: 38906738 DOI: 10.1016/j.tig.2024.05.010] [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: 04/12/2024] [Revised: 05/28/2024] [Accepted: 05/29/2024] [Indexed: 06/23/2024]
Abstract
Cell-cell interactions orchestrate complex functions in multicellular organisms, forming a regulatory network for diverse biological processes. Their disruption leads to disease states. Recent advancements - including single-cell sequencing and spatial transcriptomics, coupled with powerful bioengineering and molecular tools - have revolutionized our understanding of how cells respond to each other. Notably, spatial transcriptomics allows us to analyze gene expression changes based on cell proximity, offering a unique window into the impact of cell-cell contact. Additionally, computational approaches are being developed to decipher how cell contact governs the symphony of cellular responses. This review explores these cutting-edge approaches, providing valuable insights into deciphering the intricate cellular changes influenced by cell-cell communication.
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Affiliation(s)
- Hyobin Kim
- Department of Computational Biomedicine, Cedars-Sinai Medical Center, West, Hollywood, CA, USA
| | - Kwang-Eun Kim
- Department of Convergence Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea; Department of Chemistry, Seoul National University, Seoul, South Korea
| | - Esha Madan
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA; School of Medicine, Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA, USA; Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Patrick Martin
- Department of Computational Biomedicine, Cedars-Sinai Medical Center, West, Hollywood, CA, USA
| | - Rajan Gogna
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA; School of Medicine, Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA, USA; Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Hyun-Woo Rhee
- Department of Chemistry, Seoul National University, Seoul, South Korea.
| | - Kyoung-Jae Won
- Department of Computational Biomedicine, Cedars-Sinai Medical Center, West, Hollywood, CA, USA.
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Wu Y, Yi J, Zhang Q. Analysis of dietary inflammatory potential and mortality in cancer survivors using NHANES data. Front Nutr 2024; 11:1467259. [PMID: 39346654 PMCID: PMC11427406 DOI: 10.3389/fnut.2024.1467259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 08/29/2024] [Indexed: 10/01/2024] Open
Abstract
Background In the United States, cancer is a leading cause of mortality, with inflammation playing a crucial role in cancer progression and prognosis. Diet, with its capacity to modulate inflammatory responses, represents a potentially modifiable risk factor in cancer outcomes. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES, 1999-2018) to investigate the association between the Dietary Inflammatory Index (DII), which reflects dietary-induced inflammation, and mortality among cancer survivors. A total of 3,011 participants diagnosed with cancer were included, with DII scores derived from dietary recall data. All-cause and cancer-related mortalities served as primary endpoints. Results The study identified a significant linear positive correlation between higher DII scores and all-cause mortality among cancer survivors. Each unit increase in DII was associated with a 10% higher risk of all-cause mortality (hazard ratio [HR] per 1-unit increase, 1.10; 95% confidence interval [CI], 1.04-1.15). Similarly, a unit increase in DII was associated with a 13% higher risk of cancer-related mortality (HR per 1-unit increase, 1.13; 95% CI, 1.02-1.25). Kaplan-Meier analyses demonstrated higher all-cause mortality rates in individuals with elevated DII scores. Sensitivity analyses confirmed the robustness of these findings. Conclusion Adoption of an anti-inflammatory diet, characterized by lower DII scores, may improve survival outcomes in cancer survivors. These results emphasize the critical role of dietary interventions in post-cancer care.
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Affiliation(s)
- Yemei Wu
- Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Yi
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qu Zhang
- Department of Radiotherapy Center, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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10
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Wang C, Yuan J, Yu H, Lin J, Bai B. Identification of Hub Genes in Comorbidity of Psoriasis and Vitiligo Using Bioinformatics Analysis. Clin Cosmet Investig Dermatol 2024; 17:2021-2037. [PMID: 39258216 PMCID: PMC11386070 DOI: 10.2147/ccid.s470149] [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: 03/24/2024] [Accepted: 08/05/2024] [Indexed: 09/12/2024]
Abstract
Background Psoriasis and vitiligo are two common autoimmune skin diseases with increased risk of comorbidities, but the common molecular mechanism about the occurrence of these two diseases is still unknown. Objective This study aimed to identify the combined genetic profiles and evaluate the potential mechanism underlying the occurrence of this complication. Methods The Gene Expression Omnibus (GEO) database was used to obtain the gene expression profiles of psoriasis (GSE30999) and vitiligo (GSE75819), and common differentially expressed genes (DEGs) were identified using GEO2R. DEGs were analyzed using functional enrichment analysis, protein-protein interaction (PPI) network and module construction, hub gene identification, and co-expression analysis. And hub genes were identified using Cytoscape software, and the gene expression of hub genes were validated in psoriasis (GSE13355) and vitiligo (GSE65127) datasets and immunohistochemistry at the clinical sample. Results A total of 164 common DEGs with the same trend (137 upregulated and 27 downregulated) were selected for subsequent analysis. Functional analysis emphasized the important roles of the cell cycle and mitotic cell division, cytoskeletal reorganization, and chromatin remodeling in the complications of these two diseases. Fourteen important hub genes were identified, including BUB1, CEP55, CDK1, TOP2A, CENPF, PBK, MELK, CCNB2, MAD2L1, NUSAP1, TTK, NEK2, CDKN3, and PTTG1. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) may be an important immune checkpoint in the pathogenesis of the comorbidities. Conclusion Our study identified hub genes and potential mechanisms underlying psoriasis and vitiligo complications. And we proposed a new spatio-temporal theory and the probable immune checkpoint for the pathogenesis of the comorbidity which may provide new ideas for the further research.
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Affiliation(s)
- Chen Wang
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Jinping Yuan
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Huiwen Yu
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Jiaying Lin
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Bingxue Bai
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
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Zheng Y, Li J, Xu D, Liu L, Li Y, Yi J, Dong J, Pang D, Tang H. Tunneling nanotubes mediate KRas transport: Inducing tumor heterogeneity and altering cellular membrane mechanical properties. Acta Biomater 2024; 185:312-322. [PMID: 38969079 DOI: 10.1016/j.actbio.2024.06.046] [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: 02/11/2024] [Revised: 06/17/2024] [Accepted: 06/27/2024] [Indexed: 07/07/2024]
Abstract
Mutation in oncogene KRas plays a crucial role in the occurrence and progression of numerous malignant tumors. Malignancy involves changes in cell mechanics for extensive cellular deformation during metastatic dissemination. We hypothesize that oncogene KRas mutations are intrinsic to alterations in cellular mechanics that promote malignant tumor generation and progression. Here, we demonstrate the use of optical tweezers coupled with a confocal fluorescence imaging system and gene interference technique to reveal that the mutant KRas protein can be transported between homogeneous and heterogeneous tumor cells by tunneling nanotubes (TNTs), resulting in a significant reduction of membrane tension and acceleration of membrane phospholipid flow in the recipient cells. Simultaneously, the changes in membrane mechanical properties of the tumor cells also enhance the metastatic and invasive ability of the tumors, which further contribute to the deterioration of the tumors. This finding helps to clarify the association between oncogene mutations and changes in the mechanical properties of tumor cells, which provides a theoretical basis for the development of cancer treatment strategies. STATEMENT OF SIGNIFICANCE: Here, we present a laser confocal fluorescence system integrated with optical tweezers to observe the transfer of mutant KRasG12D protein from mutant cells to wild-type cells through TNTs. Malignancy involves changes in cell mechanics for extensive cellular deformation during metastatic dissemination. Our results demonstrate a significant decrease in membrane tension and an increase in membrane phospholipid flow in recipient cells. These alterations in mechanical properties augment the migration and invasive capabilities of tumor cells, contributing to tumor malignancy. Our findings propose that cellular mechanical properties could serve as new markers for tumor development, and targeting membrane tension may hold potential as a therapeutic strategy.
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Affiliation(s)
- Yawen Zheng
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China
| | - Jiangtao Li
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China
| | - Dadi Xu
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China
| | - Liu Liu
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China
| | - Yuyao Li
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China
| | - Jing Yi
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China
| | - Jiayao Dong
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China
| | - Daiwen Pang
- College of Chemistry, Nankai University, Tianjin, 300071, PR China
| | - Hongwu Tang
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China.
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12
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Metzner KL, Fang Q, Sanderson RW, Yeow YL, Green C, Abdul-Aziz F, Hamzah J, Mowla A, Kennedy BF. A novel stress sensor enables accurate estimation of micro-scale tissue mechanics in quantitative micro-elastography. APL Bioeng 2024; 8:036115. [PMID: 39319307 PMCID: PMC11421860 DOI: 10.1063/5.0220309] [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: 05/24/2024] [Accepted: 09/10/2024] [Indexed: 09/26/2024] Open
Abstract
Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique enabling the estimation of tissue mechanical properties on the micro-scale. QME utilizes a compliant layer as an optical stress sensor, placed between an imaging window and tissue, providing quantitative estimation of elasticity. However, the implementation of the layer is challenging and introduces unpredictable friction conditions at the contact boundaries, deteriorating the accuracy and reliability of elasticity estimation. This has largely limited the use of QME to ex vivo studies and is a barrier to clinical translation. In this work, we present a novel implementation by affixing the stress sensing layer to the imaging window and optimizing the layer thickness, enhancing the practical use of QME for in vivo applications by eliminating the requirement for manual placement of the layer, and significantly reducing variations in the friction conditions, leading to substantial improvement in the accuracy and repeatability of elasticity estimation. We performed a systematic validation of the integrated layer, demonstrating >30% improvement in sensitivity and the ability to provide mechanical contrast in a mechanically heterogeneous phantom. In addition, we demonstrate the ability to obtain accurate estimation of elasticity (<6% error compared to <14% achieved using existing QME) in homogeneous phantoms with mechanical properties ranging from 40 to 130 kPa. Furthermore, we show the integrated layer to be more robust, exhibiting increased temporal stability, as well as improved conformity to variations in sample surface topography, allowing for accurate estimation of elasticity over acquisition times 3× longer than current methods. Finally, when applied to ex vivo human breast tissue, we demonstrate the ability to distinguish between healthy and diseased tissue features, such as stroma and cancer, confirmed by co-registered histology, showcasing the potential for routine use in biomedical applications.
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Affiliation(s)
| | | | | | - Yen L Yeow
- Systems Biology and Genomics Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia and Centre for Medical Research, The University of Western Australia, Perth, Western Australia 6009, Australia
| | - Celia Green
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, Western Australia 6009, Australia
| | - Farah Abdul-Aziz
- Hollywood Private Hospital, Nedlands, Western Australia 6009, Australia
| | - Juliana Hamzah
- Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia
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13
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Gui Y, Deng X, Li N, Zhao L. PRELP reduce cell stiffness and adhesion to promote the growth and metastasis of colorectal cancer cells by binding to integrin α5. Exp Cell Res 2024; 441:114151. [PMID: 38992455 DOI: 10.1016/j.yexcr.2024.114151] [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: 12/14/2023] [Revised: 06/19/2024] [Accepted: 07/03/2024] [Indexed: 07/13/2024]
Abstract
PRELP is thought to be an inhibitor of the development and progression of a variety of malignancies. Metastasis is a major cause of death in patients with colorectal cancer, but the mechanism underlying the role of PRELP in colorectal cancer metastasis remains poorly understood. In this study, we found that PRELP was significantly higher in metastatic tissues than in non-metastatic tissues of colorectal cancer and was closely associated with poor prognosis of colorectal cancer patients. PRELP promotes growth and metastasis of colorectal cancer cells. PRELP reduces cell stiffness and adhesion. PRELP promoted EMT in colorectal cancer cells and that PRELP bind to integrin α5 to activate the integrin α5/FAK/AKT signaling pathway. In conclusion, we demonstrate that PRELP is upregulated in metastatic colorectal cancer, providing a potential prognostic marker and therapeutic target for the clinical management of metastatic colorectal cancer from a biomechanical perspective.
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Affiliation(s)
- Yajun Gui
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 41001l, China; Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha, Human, 410011, China
| | - Xiangying Deng
- Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Namei Li
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 41001l, China; Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha, Human, 410011, China
| | - Lin Zhao
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 41001l, China; Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha, Human, 410011, China.
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14
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Hou X, Ouyang J, Tang L, Wu P, Deng X, Yan Q, Shi L, Fan S, Fan C, Guo C, Liao Q, Li Y, Xiong W, Li G, Zeng Z, Wang F. KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation. PLoS Biol 2024; 22:e3002666. [PMID: 38905316 PMCID: PMC11192366 DOI: 10.1371/journal.pbio.3002666] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 05/07/2024] [Indexed: 06/23/2024] Open
Abstract
Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.
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Affiliation(s)
- Xiangchan Hou
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Jiawei Ouyang
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Le Tang
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Pan Wu
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Xiangying Deng
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Qijia Yan
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lei Shi
- Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Songqing Fan
- Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chunmei Fan
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Can Guo
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Qianjin Liao
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yong Li
- Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Fuyan Wang
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
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15
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Li M. Harnessing atomic force microscopy-based single-cell analysis to advance physical oncology. Microsc Res Tech 2024; 87:631-659. [PMID: 38053519 DOI: 10.1002/jemt.24467] [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: 08/22/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 12/07/2023]
Abstract
Single-cell analysis is an emerging and promising frontier in the field of life sciences, which is expected to facilitate the exploration of fundamental laws of physiological and pathological processes. Single-cell analysis allows experimental access to cell-to-cell heterogeneity to reveal the distinctive behaviors of individual cells, offering novel opportunities to dissect the complexity of severe human diseases such as cancers. Among the single-cell analysis tools, atomic force microscopy (AFM) is a powerful and versatile one which is able to nondestructively image the fine topographies and quantitatively measure multiple mechanical properties of single living cancer cells in their native states under aqueous conditions with unprecedented spatiotemporal resolution. Over the past few decades, AFM has been widely utilized to detect the structural and mechanical behaviors of individual cancer cells during the process of tumor formation, invasion, and metastasis, yielding numerous unique insights into tumor pathogenesis from the biomechanical perspective and contributing much to the field of cancer mechanobiology. Here, the achievements of AFM-based analysis of single cancer cells to advance physical oncology are comprehensively summarized, and challenges and future perspectives are also discussed. RESEARCH HIGHLIGHTS: Achievements of AFM in characterizing the structural and mechanical behaviors of single cancer cells are summarized, and future directions are discussed. AFM is not only capable of visualizing cellular fine structures, but can also measure multiple cellular mechanical properties as well as cell-generated mechanical forces. There is still plenty of room for harnessing AFM-based single-cell analysis to advance physical oncology.
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Affiliation(s)
- Mi Li
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, China
- Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang, China
- University of Chinese Academy of Sciences, Beijing, China
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16
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Ferraguti G, Terracina S, Tarani L, Fanfarillo F, Allushi S, Caronti B, Tirassa P, Polimeni A, Lucarelli M, Cavalcanti L, Greco A, Fiore M. Nerve Growth Factor and the Role of Inflammation in Tumor Development. Curr Issues Mol Biol 2024; 46:965-989. [PMID: 38392180 PMCID: PMC10888178 DOI: 10.3390/cimb46020062] [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: 12/06/2023] [Revised: 01/12/2024] [Accepted: 01/19/2024] [Indexed: 02/24/2024] Open
Abstract
Nerve growth factor (NGF) plays a dual role both in inflammatory states and cancer, acting both as a pro-inflammatory and oncogenic factor and as an anti-inflammatory and pro-apoptotic mediator in a context-dependent way based on the signaling networks and its interaction with diverse cellular components within the microenvironment. This report aims to provide a summary and subsequent review of the literature on the role of NGF in regulating the inflammatory microenvironment and tumor cell growth, survival, and death. The role of NGF in inflammation and tumorigenesis as a component of the inflammatory system, its interaction with the various components of the respective microenvironments, its ability to cause epigenetic changes, and its role in the treatment of cancer have been highlighted in this paper.
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Affiliation(s)
- Giampiero Ferraguti
- Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Sergio Terracina
- Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Luigi Tarani
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy
| | - Francesca Fanfarillo
- Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Sara Allushi
- Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Brunella Caronti
- Department of Human Neurosciences, Sapienza University Hospital of Rome, 00185 Rome, Italy
| | - Paola Tirassa
- Institute of Biochemistry and Cell Biology (IBBC-CNR), Department of Sensory Organs, Sapienza University of Rome, 00185 Rome, Italy
| | - Antonella Polimeni
- Department of Odontostomatological and Maxillofacial Sciences, Sapienza University of Rome, 00185 Rome, Italy
| | - Marco Lucarelli
- Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
- Pasteur Institute, Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, Italy
| | - Luca Cavalcanti
- Department of Sensory Organs, Sapienza University of Rome, 00185 Rome, Italy
| | - Antonio Greco
- Department of Sensory Organs, Sapienza University of Rome, 00185 Rome, Italy
| | - Marco Fiore
- Institute of Biochemistry and Cell Biology (IBBC-CNR), Department of Sensory Organs, Sapienza University of Rome, 00185 Rome, Italy
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17
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Mierke CT. Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells. Cells 2024; 13:96. [PMID: 38201302 PMCID: PMC10777970 DOI: 10.3390/cells13010096] [Citation(s) in RCA: 34] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 12/29/2023] [Accepted: 01/01/2024] [Indexed: 01/12/2024] Open
Abstract
Extracellular biophysical properties have particular implications for a wide spectrum of cellular behaviors and functions, including growth, motility, differentiation, apoptosis, gene expression, cell-matrix and cell-cell adhesion, and signal transduction including mechanotransduction. Cells not only react to unambiguously mechanical cues from the extracellular matrix (ECM), but can occasionally manipulate the mechanical features of the matrix in parallel with biological characteristics, thus interfering with downstream matrix-based cues in both physiological and pathological processes. Bidirectional interactions between cells and (bio)materials in vitro can alter cell phenotype and mechanotransduction, as well as ECM structure, intentionally or unintentionally. Interactions between cell and matrix mechanics in vivo are of particular importance in a variety of diseases, including primarily cancer. Stiffness values between normal and cancerous tissue can range between 500 Pa (soft) and 48 kPa (stiff), respectively. Even the shear flow can increase from 0.1-1 dyn/cm2 (normal tissue) to 1-10 dyn/cm2 (cancerous tissue). There are currently many new areas of activity in tumor research on various biological length scales, which are highlighted in this review. Moreover, the complexity of interactions between ECM and cancer cells is reduced to common features of different tumors and the characteristics are highlighted to identify the main pathways of interaction. This all contributes to the standardization of mechanotransduction models and approaches, which, ultimately, increases the understanding of the complex interaction. Finally, both the in vitro and in vivo effects of this mechanics-biology pairing have key insights and implications for clinical practice in tumor treatment and, consequently, clinical translation.
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Affiliation(s)
- Claudia Tanja Mierke
- Biological Physics Division, Peter Debye Institute of Soft Matter Physics, Faculty of Physics and Earth Science, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany
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18
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Dai Y, Yu C, Zhou L, Cheng L, Ni H, Liang W. Chemokine receptor CXCR4 interacts with nuclear receptor Nur77 and promote glioma invasion and progression. Brain Res 2024; 1822:148647. [PMID: 37890573 DOI: 10.1016/j.brainres.2023.148647] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 10/15/2023] [Accepted: 10/23/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND Glioma is the most common primary brain tumor. It is prone to progress and have high rate of mortality regardless of radiation or chemotherapy due to its invasive growth features. Chemokine and its receptor CXCL12 and CXCR4 play important roles in cancer metastasis. METHODS In this study, we investigate the role of CXCR4 in the progression of glioma by various molecular technologies, including qRT-PCR, Western blotting, wound closure assay, transwell assay et al. RESULTS: It was found that CXCR4 was overexpressed in glioma tissues. The expression of CXCR4 was correlated with patients' overall survival. Wound closure assay and transwell invasion assay showed that inhibition of CXCR4 significantly reduced the expression of biomarkers related to the formation of invadopodium, leading to decrease the invasion and migration of glioma tumor cells. Knocking down the nuclear receptor Nur77 remarkably decreased CXCR4 expression and reduced glioma cell invasion and migration. The reduction of glioma cell invasion and migration were observed after Nur77 inhibitor treatment. CONCLUSION Taken together, these results indicated that CXCR4 is critical in promoting glioma migration and invasion. Inhibition of Nur77 reduces CXCR4 related cancer progression.
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Affiliation(s)
- Yuxiang Dai
- Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China
| | - Chen Yu
- Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, China
| | - Lu Zhou
- Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China
| | - Longyang Cheng
- Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China
| | - Hongbin Ni
- Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China
| | - Weibang Liang
- Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, China.
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19
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Mierke CT. Editorial: Cancer cell adhesion, metastasis, and the immune response. Front Cell Dev Biol 2023; 11:1347446. [PMID: 38149047 PMCID: PMC10749920 DOI: 10.3389/fcell.2023.1347446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 12/05/2023] [Indexed: 12/28/2023] Open
Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth Systems Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, Leipzig University, Leipzig, Germany
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20
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Mierke CT. Editorial: In celebration of women in cell adhesion and migration. Front Cell Dev Biol 2023; 11:1348958. [PMID: 38146493 PMCID: PMC10749420 DOI: 10.3389/fcell.2023.1348958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 12/05/2023] [Indexed: 12/27/2023] Open
Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth Systems Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, Leipzig University, Leipzig, Germany
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21
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Zhang YZ, Li MZ, Wang GX, Wang DW. Bibliometric analysis of the global research status and trends of mechanotransduction in cancer. World J Clin Oncol 2023; 14:518-534. [PMID: 38059188 PMCID: PMC10696219 DOI: 10.5306/wjco.v14.i11.518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/14/2023] [Accepted: 10/16/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND The development of cancer is thought to involve the dynamic crosstalk between the tumor cells and the microenvironment they inhabit. Such crosstalk is thought to involve mechanotransduction, a process whereby the cells sense mechanical cues such as stiffness, and translate these into biochemical signals, which have an impact on the subsequent cellular activities. Bibliometric analysis is a statistical method that involves investigating different aspects (including authors' names and affiliations, article keywords, journals and citations) of large volumes of literature. Despite an increase in mechanotransduction-related research in recent years, there are currently no bibliometric studies that describe the global status and trends of mechanotransduction-related research in the cancer field. AIM To investigate the global research status and trends of mechanotransduction in cancer from a bibliometric viewpoint. METHODS Literature on mechanotransduction in cancer published from January 1, 1900 to December 31, 2022 was retrieved from the Web of Science Core Collection. Excel and GraphPad software carried out the statistical analysis of the relevant author, journal, organization, and country information. The co-authorship, keyword co-occurrence, and keyword burst analysis were visualized with VOSviewer and CiteSpace. RESULTS Of 597 publications from 745 institutions in 45 countries were published in 268 journals with 35510 citation times. With 270 articles, the United States is a well-established global leader in this field, and the University of California system, the most productive (n = 36) and influential institution (n = 4705 citations), is the most highly active in collaborating with other organizations. Cancers was the most frequent publisher with the highest H-index. The most productive researcher was Valerie M. Weaver, with 10 publications. The combined analysis of concurrent and burst keywords revealed that the future research hotspots of mechanotransduction in cancer were related to the plasma membrane, autophagy, piezo1/2, heterogeneity, cancer diagnosis, and post-transcriptional modifications. CONCLUSION Mechanotransduction-related cancer research remains a hot topic. The United States is in the leading position of global research on mechano-oncology after almost 30 years of investigations. Research group cooperations exist but remain largely domestic, lacking cross-national communications. The next big topic in this field is to explore how the plasma membrane and its localized mechanosensor can transduce mechanical force through post-transcriptional modifications and thereby participate in cellular activity regulations and cancer development.
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Affiliation(s)
- Yi-Zhan Zhang
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong Province, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan 250021, Shandong Province, China
| | - Meng-Zhu Li
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong Province, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan 250021, Shandong Province, China
| | - Guang-Xin Wang
- Shandong Innovation Center of Intelligent Diagnosis, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Da-Wei Wang
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong Province, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan 250021, Shandong Province, China
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22
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Herrera-Reinoza N, Tortelli Junior TC, Teixeira FDS, Chammas R, Salvadori MC. Role of galectin-3 in the elastic response of radial growth phase melanoma cancer cells. Microsc Res Tech 2023; 86:1353-1362. [PMID: 37070727 DOI: 10.1002/jemt.24328] [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: 09/14/2022] [Revised: 02/28/2023] [Accepted: 04/06/2023] [Indexed: 04/19/2023]
Abstract
Melanoma is originated from the malignant transformation of the melanocytes and is characterized by a high rate of invasion, the more serious stage compromising deeper layers of the skin and eventually leading to the metastasis. A high mortality due to melanoma lesion persists because most of melanoma lesions are detected in advanced stages, which decreases the chances of survival. The identification of the principal mechanics implicated in the development and progression of melanoma is essential to devise new early diagnosis strategies. Cell mechanics is related with a lot of cellular functions and processes, for instance motility, differentiation, migration and invasion. In particular, the elastic modulus (Young's modulus) is a very explored parameter to describe the cell mechanical properties; most cancer cells reported in the literature smaller elasticity modulus. In this work, we show that the elastic modulus of melanoma cells lacking galectin-3 is significantly lower than those of melanoma cells expressing galectin-3. More interestingly, the gradient of elastic modulus in cells from the nuclear region towards the cell periphery is more pronounced in shGal3 cells. RESEARCH HIGHLIGHTS: AFM imaging and force spectroscopy were used to investigate the morphology and elasticity properties of healthy HaCaT cells and melanoma cells WM1366, with (shSCR) and without (shGal3) expression of galectin-3. It is shown the effect of galectin-3 protein on the elastic properties of cells: the cells without expression of galectin-3 presents lower elastic modulus. By the results, we suggest here that galectin-3 could be used as an effective biomarker of malignancy in both melanoma diagnostic and prognosis.
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Affiliation(s)
| | | | | | - Roger Chammas
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina de São Paulo, São Paulo, Brazil
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23
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Amiri A, Dietz C, Rapp A, Cardoso MC, Stark RW. The cyto-linker and scaffolding protein "plectin" mis-localization leads to softening of cancer cells. NANOSCALE 2023; 15:15008-15026. [PMID: 37668423 DOI: 10.1039/d3nr02226a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/06/2023]
Abstract
Discovering tools to prevent cancer progression requires understanding the fundamental differences between normal and cancer cells. More than a decade ago, atomic force microscopy (AFM) revealed cancer cells' softer body compared to their healthy counterparts. Here, we investigated the mechanism underlying the softening of cancerous cells in comparison with their healthy counterparts based on AFM high resolution stiffness tomography and 3D confocal microscopy. We showed microtubules (MTs) network in invasive ductal carcinoma cell cytoskeleton is basally located and segmented for around 400 nm from the cell periphery. Additionally, the cytoskeleton scaffolding protein plectin exhibits a mis-localization from the cytoplasm to the surface of cells in the carcinoma which justifies the dissociation of the MT network from the cell's cortex. Furthermore, the assessment of MTs' persistence length using a worm-like-chain (WLC) model in high resolution AFM images showed lower persistence length of the single MTs in ductal carcinoma compared to that in the normal state. Overall, these tuned mechanics support the invasive cells to ascertain more flexibility under compressive forces in small deformations. These data provide new insights into the structural origins of cancer aids in progression.
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Affiliation(s)
- Anahid Amiri
- Physics of Surfaces, Institute of Materials Science, Technical University of Darmstadt, Alarich-Weiss-Str. 2, 64287 Darmstadt, Germany.
| | - Christian Dietz
- Physics of Surfaces, Institute of Materials Science, Technical University of Darmstadt, Alarich-Weiss-Str. 2, 64287 Darmstadt, Germany.
| | - Alexander Rapp
- Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany
| | - M Cristina Cardoso
- Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany
| | - Robert W Stark
- Physics of Surfaces, Institute of Materials Science, Technical University of Darmstadt, Alarich-Weiss-Str. 2, 64287 Darmstadt, Germany.
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24
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Mierke CT. Editorial: Editorial for mechanical and structural phenotypes of cells and extracellular matrices govern cell adhesion and migration. Front Cell Dev Biol 2023; 11:1256311. [PMID: 37576605 PMCID: PMC10420056 DOI: 10.3389/fcell.2023.1256311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 07/17/2023] [Indexed: 08/15/2023] Open
Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, Leipzig University, Leipzig, Germany
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25
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Régnier L, Bénichou O, Krapivsky PL. Range-Controlled Random Walks. PHYSICAL REVIEW LETTERS 2023; 130:227101. [PMID: 37327439 DOI: 10.1103/physrevlett.130.227101] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 04/03/2023] [Accepted: 05/09/2023] [Indexed: 06/18/2023]
Abstract
We introduce range-controlled random walks with hopping rates depending on the range N, that is, the total number of previously distinct visited sites. We analyze a one-parameter class of models with a hopping rate N^{a} and determine the large time behavior of the average range, as well as its complete distribution in two limit cases. We find that the behavior drastically changes depending on whether the exponent a is smaller, equal, or larger than the critical value, a_{d}, depending only on the spatial dimension d. When a>a_{d}, the forager covers the infinite lattice in a finite time. The critical exponent is a_{1}=2 and a_{d}=1 when d≥2. We also consider the case of two foragers who compete for food, with hopping rates depending on the number of sites each visited before the other. Surprising behaviors occur in 1D where a single walker dominates and finds most of the sites when a>1, while for a<1, the walkers evenly explore the line. We compute the gain of efficiency in visiting sites by adding one walker.
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Affiliation(s)
- L Régnier
- Laboratoire de Physique Théorique de la Matière Condensée, CNRS/Sorbonne Université, 75005 Paris, France
| | - O Bénichou
- Laboratoire de Physique Théorique de la Matière Condensée, CNRS/Sorbonne Université, 75005 Paris, France
| | - P L Krapivsky
- Department of Physics, Boston University, Boston, Massachusetts 02215, USA
- Santa Fe Institute, Santa Fe, New Mexico 87501, USA
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26
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Nguyen TH, Nguyen HA, Tran Thi YV, Hoang Tran D, Cao H, Chu Duc T, Bui TT, Do Quang L. Concepts, electrode configuration, characterization, and data analytics of electric and electrochemical microfluidic platforms: a review. Analyst 2023; 148:1912-1929. [PMID: 36928639 DOI: 10.1039/d2an02027k] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
Abstract
Microfluidic cytometry (MC) and electrical impedance spectroscopy (EIS) are two important techniques in biomedical engineering. Microfluidic cytometry has been utilized in various fields such as stem cell differentiation and cancer metastasis studies, and provides a simple, label-free, real-time method for characterizing and monitoring cellular fates. The impedance microdevice, including impedance flow cytometry (IFC) and electrical impedance spectroscopy (EIS), is integrated into MC systems. IFC measures the impedance of individual cells as they flow through a microfluidic device, while EIS measures impedance changes during binding events on electrode regions. There have been significant efforts to improve and optimize these devices for both basic research and clinical applications, based on the concepts, electrode configurations, and cell fates. This review outlines the theoretical concepts, electrode engineering, and data analytics of these devices, and highlights future directions for development.
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Affiliation(s)
- Thu Hang Nguyen
- University of Engineering and Technology, Vietnam National University, Hanoi, Vietnam.
| | | | - Y-Van Tran Thi
- University of Science, Vietnam National University, Hanoi, Vietnam.
| | | | - Hung Cao
- University of California, Irvine, USA
| | - Trinh Chu Duc
- University of Engineering and Technology, Vietnam National University, Hanoi, Vietnam.
| | - Tung Thanh Bui
- University of Engineering and Technology, Vietnam National University, Hanoi, Vietnam.
| | - Loc Do Quang
- University of Science, Vietnam National University, Hanoi, Vietnam.
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27
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Liu JP, Liu SC, Hu SQ, Lu JF, Wu CL, Hu DX, Zhang WJ. ATP ion channel P2X purinergic receptors in inflammation response. Biomed Pharmacother 2023; 158:114205. [PMID: 36916431 DOI: 10.1016/j.biopha.2022.114205] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/19/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023] Open
Abstract
Different studies have confirmed that P2X purinergic receptors play a key role in inflammation. Activation of P2X purinergic receptors can release inflammatory cytokines and participate in the progression of inflammatory diseases. In an inflammatory microenvironment, cells can release a large amount of ATP to activate P2X receptors, open non-selective cation channels, activate multiple intracellular signaling, release multiple inflammatory cytokines, amplify inflammatory response. While P2X4 and P2X7 receptors play an important role in the process of inflammation. P2X4 receptor can mediate the activation of microglia involved in neuroinflammation, and P2X7 receptor can mediate different inflammatory cells to mediate the progression of tissue-wide inflammation. At present, the role of P2X receptors in inflammatory response has been widely recognized and affirmed. Therefore, in this paper, we discussed the role of P2X receptors-mediated inflammation. Moreover, we also described the effects of some antagonists (such as A-438079, 5-BDBD, A-804598, A-839977, and A-740003) on inflammation relief by antagonizing the activities of P2X receptors.
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Affiliation(s)
- Ji-Peng Liu
- Department of Gastrointestinal surgery, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China
| | - Si-Cheng Liu
- Department of Gastrointestinal surgery, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China
| | - Shi-Qi Hu
- Queen Mary College, Nanchang University, Nanchang City, Jiangxi Province 343000, China
| | - Jia-Feng Lu
- Basic medical school, Nanchang University, Nanchang City, Jiangxi Province 343000, China
| | - Chang-Lei Wu
- Department of Gastrointestinal surgery, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China
| | - Dong-Xia Hu
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China.
| | - Wen-Jun Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China.
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28
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Zills G, Datta T, Malmi-Kakkada AN. Enhanced mechanical heterogeneity of cell collectives due to temporal fluctuations in cell elasticity. Phys Rev E 2023; 107:014401. [PMID: 36797877 DOI: 10.1103/physreve.107.014401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 12/08/2022] [Indexed: 06/18/2023]
Abstract
Cells are dynamic systems characterized by temporal variations in biophysical properties such as stiffness and contractility. Recent studies show that the recruitment and release of actin filaments into and out of the cell cortex-a network of proteins underneath the cell membrane-leads to cell stiffening prior to division and softening immediately afterward. In three-dimensional (3D) cell collectives, it is unclear whether the stiffness change during division at the single-cell scale controls the spatial structure and dynamics at the multicellular scale. This is an important question to understand because cell stiffness variations impact cell spatial organization and cancer progression. Using a minimal 3D model incorporating cell birth, death, and cell-to-cell elastic and adhesive interactions, we investigate the effect of mechanical heterogeneity-variations in individual cell stiffnesses that make up the cell collective-on tumor spatial organization and cell dynamics. We discover that spatial mechanical heterogeneity characterized by a spheroid core composed of stiffer cells and softer cells in the periphery emerges within dense 3D cell collectives, which may be a general feature of multicellular tumor growth. We show that heightened spatial mechanical heterogeneity enhances single-cell dynamics and volumetric tumor growth driven by fluctuations in cell elasticity. Our results could have important implications in understanding how spatiotemporal variations in single-cell stiffness determine tumor growth and spread.
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Affiliation(s)
- Garrett Zills
- Department of Chemistry and Physics, Augusta University, 1120 15th Street, Augusta, Georgia 30912, USA
| | - Trinanjan Datta
- Department of Chemistry and Physics, Augusta University, 1120 15th Street, Augusta, Georgia 30912, USA
- Kavli Institute for Theoretical Physics, University of California, Santa Barbara, California 93106, USA
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29
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Xia F, Youcef-Toumi K. Review: Advanced Atomic Force Microscopy Modes for Biomedical Research. BIOSENSORS 2022; 12:1116. [PMID: 36551083 PMCID: PMC9775674 DOI: 10.3390/bios12121116] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/20/2022] [Accepted: 11/22/2022] [Indexed: 06/17/2023]
Abstract
Visualization of biomedical samples in their native environments at the microscopic scale is crucial for studying fundamental principles and discovering biomedical systems with complex interaction. The study of dynamic biological processes requires a microscope system with multiple modalities, high spatial/temporal resolution, large imaging ranges, versatile imaging environments and ideally in-situ manipulation capabilities. Recent development of new Atomic Force Microscopy (AFM) capabilities has made it such a powerful tool for biological and biomedical research. This review introduces novel AFM functionalities including high-speed imaging for dynamic process visualization, mechanobiology with force spectroscopy, molecular species characterization, and AFM nano-manipulation. These capabilities enable many new possibilities for novel scientific research and allow scientists to observe and explore processes at the nanoscale like never before. Selected application examples from recent studies are provided to demonstrate the effectiveness of these AFM techniques.
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30
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Chen CJ, Lee CT, Tsai YN, Tseng CM, Chen TH, Hsu MH, Wang CC, Wang WL. Prognostic significance of systemic inflammatory response markers in patients with superficial esophageal squamous cell carcinomas. Sci Rep 2022; 12:18241. [PMID: 36309551 PMCID: PMC9617918 DOI: 10.1038/s41598-022-21974-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 10/07/2022] [Indexed: 12/31/2022] Open
Abstract
Endoscopic resection or esophagectomy has becoming the standard treatment for superficial esophageal squamous cell carcinomas (SESCC), but some patients may develop disease progression or second primary cancers after the therapies. Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) reflect the balance between pro-cancer inflammatory and anti-cancer immune responses, however their roles in SESCC are still unknown. We consecutively enrolled patients with newly diagnosed SESCC (clinical stage Tis or T1N0M0) who were treated at our institute. Pre-treatment NLR, LMR and PLR were assessed and then correlated with clinical factors and long-term survival. A total of 156 patients were enrolled (152 males, 4 females; median age: 52.2 years), of whom 104 received endoscopic resection and 52 were treated with esophagectomy or chemoradiation.. During a mean follow-up period of 60.1 months, seventeen patients died of ESCCs, and 45 died of second primary cancers. The 5-year ESCC-specific survival and 5-year overall survival rate were 86% and 57%, respectively. LMR (P < 0.05) and NLR (P < 0.05), but not PLR were significantly correlated with overall survival. Receiver operating characteristic curve analysis showed optimal LMR and NLR cut-off values of 4 and 2.5, respectively, to predict a poor prognosis. Patients with a high NLR or low LMR tended to have longer tumor length, larger circumferential extension, and presence of second primary cancers. Multivariate Cox regression analysis showed that presence of second primary cancers (HR: 5.05, 95%CI: 2.75-9.28), low LMR (HR: 2.56, 95%CI: 1.09-6.03) were independent risk factors for poor survival. A low pre-treatment LMR may be a non-invasive pretreatment predictor of poor prognosis to guide the surveillance program, suggesting that anti-cancer immunity may play a role in the early events of esophageal squamous cancer.
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Affiliation(s)
- Chi-Jen Chen
- grid.411447.30000 0004 0637 1806Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan ,Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Ching-Tai Lee
- grid.411447.30000 0004 0637 1806Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan
| | - Ying-Nan Tsai
- grid.411447.30000 0004 0637 1806Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan ,Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Chao-Ming Tseng
- grid.411447.30000 0004 0637 1806Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan ,Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Tzu-Haw Chen
- grid.411447.30000 0004 0637 1806Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan
| | - Ming-Hung Hsu
- grid.411447.30000 0004 0637 1806Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan
| | - Chih-Chun Wang
- grid.411447.30000 0004 0637 1806Department of Otolaryngology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Wen-Lun Wang
- grid.411447.30000 0004 0637 1806Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan ,grid.411447.30000 0004 0637 1806School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
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31
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Jiang K, Wen X, Pettersson T, Crouzier T. Engineering Surfaces with Immune Modulating Properties of Mucin Hydrogels. ACS APPLIED MATERIALS & INTERFACES 2022; 14:39727-39735. [PMID: 36000701 PMCID: PMC9460428 DOI: 10.1021/acsami.1c19250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 08/05/2022] [Indexed: 06/15/2023]
Abstract
Hydrogels of cross-linked mucin glycoproteins (Muc-gel) have shown strong immune-modulating properties toward macrophages in vitro, which are translated in vivo by the dampening of the foreign body response to implantation in mice. Beyond mucin hydrogels, other biomaterials such as sensors, electrodes, and other long-term implants would also benefit from such immune-modulating properties. In this work, we aimed to transfer the bioactivity observed for three-dimensional Muc-gels to the surface of two model materials by immobilizing mucin into thin films (Muc-film) using covalent layer-by-layer assembly. We tested how the surface immobilization of mucins affects macrophage responses compared to Muc-gels. We showed that Muc-films on soft polyacrylamide gels mimic Muc-gel in their modulation of macrophage responses with activated gene expression of inflammatory cytokines on day 1 and then dampening them on day 3. Also, the markers of polarized macrophages, M1 and M2, were expressed at the same level for macrophages on Muc-film-coated soft polyacrylamide gels and Muc-gel. In contrast, Muc-film-coated hard polystyrene led to a different macrophage response compared to Muc-gel, having no activated expression of inflammatory cytokines and a different M1 marker expression. This suggested that the substrate mechanical properties and mucin molecular configuration determined by substrate-mucin interactions affect mucin immune-modulating properties. We conclude that mucin immune-modulating properties can be transferred to materials by mucin surface immobilization but will be dependent on the substrate chemical and mechanical properties.
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Affiliation(s)
- Kun Jiang
- Division
of Glycoscience, Department of Chemistry, School of Engineering Sciences
in Chemistry, Biotechnology and Health, KTH, Royal Institute of Technology, AlbaNova University Center, Stockholm 106 91, Sweden
- AIMES
- Center for the Advancement of Integrated Medical and Engineering
Sciences at Karolinska Institutet and KTH
Royal Institute of Technology, Stockholm SE-100 44, Sweden
- Department
of Neuroscience, Karolinska Institutet, Stockholm SE-171 77, Sweden
| | - Xueyu Wen
- Division
of Glycoscience, Department of Chemistry, School of Engineering Sciences
in Chemistry, Biotechnology and Health, KTH, Royal Institute of Technology, AlbaNova University Center, Stockholm 106 91, Sweden
| | - Torbjörn Pettersson
- Division
of Fibre Technology, Department of Fibre and Polymer Technology, School
of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm SE-100 44, Sweden
| | - Thomas Crouzier
- Division
of Glycoscience, Department of Chemistry, School of Engineering Sciences
in Chemistry, Biotechnology and Health, KTH, Royal Institute of Technology, AlbaNova University Center, Stockholm 106 91, Sweden
- AIMES
- Center for the Advancement of Integrated Medical and Engineering
Sciences at Karolinska Institutet and KTH
Royal Institute of Technology, Stockholm SE-100 44, Sweden
- Department
of Neuroscience, Karolinska Institutet, Stockholm SE-171 77, Sweden
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32
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Chen Y, Guo K, Jiang L, Zhu S, Ni Z, Xiang N. Microfluidic deformability cytometry: A review. Talanta 2022; 251:123815. [DOI: 10.1016/j.talanta.2022.123815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 07/23/2022] [Accepted: 08/02/2022] [Indexed: 10/15/2022]
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33
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Zhang T, Jia Y, Yu Y, Zhang B, Xu F, Guo H. Targeting the tumor biophysical microenvironment to reduce resistance to immunotherapy. Adv Drug Deliv Rev 2022; 186:114319. [PMID: 35545136 DOI: 10.1016/j.addr.2022.114319] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 04/28/2022] [Accepted: 04/30/2022] [Indexed: 02/06/2023]
Abstract
Immunotherapy based on immune checkpoint inhibitors has evolved into a new pillar of cancer treatment in clinics, but dealing with treatment resistance (either primary or acquired) is a major challenge. The tumor microenvironment (TME) has a substantial impact on the pathological behaviors and treatment response of many cancers. The biophysical clues in TME have recently been considered as important characteristics of cancer. Furthermore, there is mounting evidence that biophysical cues in TME play important roles in each step of the cascade of cancer immunotherapy that synergistically contribute to immunotherapy resistance. In this review, we summarize five main biophysical cues in TME that affect resistance to immunotherapy: extracellular matrix (ECM) structure, ECM stiffness, tumor interstitial fluid pressure (IFP), solid stress, and vascular shear stress. First, the biophysical factors involved in anti-tumor immunity and therapeutic antibody delivery processes are reviewed. Then, the causes of these five biophysical cues and how they contribute to immunotherapy resistance are discussed. Finally, the latest treatment strategies that aim to improve immunotherapy efficacy by targeting these biophysical cues are shared. This review highlights the biophysical cues that lead to immunotherapy resistance, also supplements their importance in related technologies for studying TME biophysical cues in vitro and therapeutic strategies targeting biophysical cues to improve the effects of immunotherapy.
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Affiliation(s)
- Tian Zhang
- Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an 710061, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Yuanbo Jia
- Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China; MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Yang Yu
- Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an 710061, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Baojun Zhang
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710049, PR China
| | - Feng Xu
- Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China; MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China.
| | - Hui Guo
- Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an 710061, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China.
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34
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King CT, Matossian MD, Savoie JJ, Nguyen K, Wright MK, Byrne CE, Elliott S, Burks HE, Bratton MR, Pashos NC, Bunnell BA, Burow ME, Collins-Burow BM, Martin EC. Liver Kinase B1 Regulates Remodeling of the Tumor Microenvironment in Triple-Negative Breast Cancer. Front Mol Biosci 2022; 9:847505. [PMID: 35755802 PMCID: PMC9214958 DOI: 10.3389/fmolb.2022.847505] [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: 01/02/2022] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
Liver kinase B1 (LKB1) is a potent tumor suppressor that regulates cellular energy balance and metabolism as an upstream kinase of the AMP-activated protein kinase (AMPK) pathway. LKB1 regulates cancer cell invasion and metastasis in multiple cancer types, including breast cancer. In this study, we evaluated LKB1’s role as a regulator of the tumor microenvironment (TME). This was achieved by seeding the MDA-MB-231-LKB1 overexpressing cell line onto adipose and tumor scaffolds, followed by the evaluation of tumor matrix-induced tumorigenesis and metastasis. Results demonstrated that the presence of tumor matrix enhanced tumorigenesis in both MDA-MB-231 and MDA-MB-231-LKB1 cell lines. Metastasis was increased in both MDA-MB-231 and -LKB1 cells seeded on the tumor scaffold. Endpoint analysis of tumor and adipose scaffolds revealed LKB1-mediated tumor microenvironment remodeling as evident through altered matrix protein production. The proteomic analysis determined that LKB1 overexpression preferentially decreased all major and minor fibril collagens (collagens I, III, V, and XI). In addition, proteins observed to be absent in tumor scaffolds in the LKB1 overexpressing cell line included those associated with the adipose matrix (COL6A2) and regulators of adipogenesis (IL17RB and IGFBP4), suggesting a role for LKB1 in tumor-mediated adipogenesis. Histological analysis of MDA-MB-231-LKB1-seeded tumors demonstrated decreased total fibril collagen and indicated decreased stromal cell presence. In accordance with this, in vitro condition medium studies demonstrated that the MDA-MB-231-LKB1 secretome inhibited adipogenesis of adipose-derived stem cells. Taken together, these data demonstrate a role for LKB1 in regulating the tumor microenvironment through fibril matrix remodeling and suppression of adipogenesis.
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Affiliation(s)
- Connor T King
- Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA, United States
| | | | - Jonathan J Savoie
- Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA, United States
| | - Khoa Nguyen
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, LA, United States
| | - Maryl K Wright
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, LA, United States
| | - C Ethan Byrne
- Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA, United States
| | - Steven Elliott
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, LA, United States
| | - Hope E Burks
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, LA, United States
| | | | - Nicholas C Pashos
- Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, LA, United States.,BioAesthetics Corporation, Durham, NC, United States
| | - Bruce A Bunnell
- Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, LA, United States
| | - Matthew E Burow
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, LA, United States.,Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, United States
| | - Bridgette M Collins-Burow
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, LA, United States
| | - Elizabeth C Martin
- Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA, United States
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Effect of Extended Lipid Core on the Hemodynamic Parameters: A Fluid-Structure Interaction Approach. Appl Bionics Biomech 2022; 2022:2047549. [PMID: 35342456 PMCID: PMC8947935 DOI: 10.1155/2022/2047549] [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: 10/16/2021] [Accepted: 02/28/2022] [Indexed: 11/17/2022] Open
Abstract
Myocardial infarction is one of the leading causes of death in the developed countries. A majority of myocardial infarctions are caused by the rupture of coronary artery plaques. In order to achieve a better understanding of the effect of the extension of the lipid core into the artery wall on the change of flow field and its effect on plaque vulnerability, we have studied the hemodynamic parameters by utilizing a finite element method and taking into account the fluid-structure interaction (FSI). Four groups of stenosis models with different sizes of lipid core were used in the study. The fully developed pulsatile velocity profile of the right coronary artery was used as the inlet boundary condition, and the pressure pulse was applied as the outlet boundary condition. The non-Newtonian Carreau model was used to simulate the non-Newtonian behavior of blood. Results indicate that the extension of the lipid core into the artery wall influences the flow field; subsequently, creates favorable conditions for additional development of the lipid core which can lead to a higher risk of plaque rupture.
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36
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Mierke CT. Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction. Front Cell Dev Biol 2022; 10:789841. [PMID: 35223831 PMCID: PMC8864183 DOI: 10.3389/fcell.2022.789841] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 01/11/2022] [Indexed: 12/13/2022] Open
Abstract
Viscoelasticity and its alteration in time and space has turned out to act as a key element in fundamental biological processes in living systems, such as morphogenesis and motility. Based on experimental and theoretical findings it can be proposed that viscoelasticity of cells, spheroids and tissues seems to be a collective characteristic that demands macromolecular, intracellular component and intercellular interactions. A major challenge is to couple the alterations in the macroscopic structural or material characteristics of cells, spheroids and tissues, such as cell and tissue phase transitions, to the microscopic interferences of their elements. Therefore, the biophysical technologies need to be improved, advanced and connected to classical biological assays. In this review, the viscoelastic nature of cytoskeletal, extracellular and cellular networks is presented and discussed. Viscoelasticity is conceptualized as a major contributor to cell migration and invasion and it is discussed whether it can serve as a biomarker for the cells' migratory capacity in several biological contexts. It can be hypothesized that the statistical mechanics of intra- and extracellular networks may be applied in the future as a powerful tool to explore quantitatively the biomechanical foundation of viscoelasticity over a broad range of time and length scales. Finally, the importance of the cellular viscoelasticity is illustrated in identifying and characterizing multiple disorders, such as cancer, tissue injuries, acute or chronic inflammations or fibrotic diseases.
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Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, University of Leipzig, Leipzig, Germany
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37
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Xie L, Du X, Wang S, Shi P, Qian Y, Zhang W, Tang X, Lin Y, Chen J, Peng L, Yu CC, Qian B. Development and evaluation of cancer differentiation analysis technology: a novel biophysics-based cancer screening method. Expert Rev Mol Diagn 2021; 22:111-117. [PMID: 34846233 DOI: 10.1080/14737159.2021.2013201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Routine health checkup is an essential strategy for monitoring population health and maintaining healthy workforces. However, there was a lack of cancer screening tests among routine health checkups due to high costs and unreliable methods. METHODS We conducted a two-stage study to evaluate the value of a blood test, Cancer Differentiation Analysis (CDATM), which is developed to differentiate the blood samples of healthy individuals from those of cancer patients through measuring and analyzing multiple biophysical properties. RESULTS The first stage of a cross-sectional study included 75,942 healthy individuals in routine health checkup, and the second stage of a prospective population-based cohort included 1,957 healthy community members. Forty-eight and ten cancer cases were identified among cross-sectional study and prospective population-based cohort, respectively. Using a pre-determined cutoff, we found that the CDA™ test could differentiate blood samples between healthy and cancer individuals with >93% specificity and >55% sensitivity in both studies. CONCLUSIONS With high specificity and moderate sensitivity of CDA™ test, our study indicates that we can analyze biophysical properties in the blood to rapidly and reliably screen healthy individuals from cancer patients in a health checkup setting where most individuals are healthy or with average risk of cancer.
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Affiliation(s)
- Li Xie
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuedong Du
- AnPac Bio-Medical Science Co., Ltd, Shanghai, China
| | - Suna Wang
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peng Shi
- Department of Statistics and Data Management, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Qian
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weituo Zhang
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xing Tang
- AnPac Bio-Medical Science Co., Ltd, Shanghai, China
| | - Yue Lin
- AnPac Bio-Medical Science Co., Ltd, Shanghai, China
| | - Jie Chen
- AnPac Bio-Medical Science Co., Ltd, Shanghai, China
| | - Lan Peng
- AnPac Bio-Medical Science Co., Ltd, Shanghai, China
| | | | - Biyun Qian
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Clinical Research Promotion and Development Center, Shanghai Hospital Development Center, Shanghai, China
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38
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Mierke CT. Viscoelasticity Acts as a Marker for Tumor Extracellular Matrix Characteristics. Front Cell Dev Biol 2021; 9:785138. [PMID: 34950661 PMCID: PMC8691700 DOI: 10.3389/fcell.2021.785138] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/23/2021] [Indexed: 12/28/2022] Open
Abstract
Biological materials such as extracellular matrix scaffolds, cancer cells, and tissues are often assumed to respond elastically for simplicity; the viscoelastic response is quite commonly ignored. Extracellular matrix mechanics including the viscoelasticity has turned out to be a key feature of cellular behavior and the entire shape and function of healthy and diseased tissues, such as cancer. The interference of cells with their local microenvironment and the interaction among different cell types relies both on the mechanical phenotype of each involved element. However, there is still not yet clearly understood how viscoelasticity alters the functional phenotype of the tumor extracellular matrix environment. Especially the biophysical technologies are still under ongoing improvement and further development. In addition, the effect of matrix mechanics in the progression of cancer is the subject of discussion. Hence, the topic of this review is especially attractive to collect the existing endeavors to characterize the viscoelastic features of tumor extracellular matrices and to briefly highlight the present frontiers in cancer progression and escape of cancers from therapy. Finally, this review article illustrates the importance of the tumor extracellular matrix mechano-phenotype, including the phenomenon viscoelasticity in identifying, characterizing, and treating specific cancer types.
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Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, University of Leipzig, Leipzig, Germany
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39
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Guo X, Li Z, Liu S, Zhang M, Guan Y, Qin J, Li X, Zhang B, Tang J. Studying the effect of PDA@CeO 2 nanoparticles with antioxidant activity on the mechanical properties of cells. J Mater Chem B 2021; 9:9204-9212. [PMID: 34698747 DOI: 10.1039/d1tb01918j] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Studying the influence of nanomaterials on the microstructure and mechanical properties of cells is essential to guide the biological applications of nanomaterials. In this article, the effects of the first synthesized PDA@CeO2 nanoparticles (NPs) with multiple ROS scavenging activities on cell ultra-morphology and mechanical properties were investigated by atomic force microscopy (AFM). After the cells were exposed to PDA@CeO2 NPs, there was no obvious change in cell morphology, but the Young's modulus of the cells was increased. On the contrary, after the cells were damaged by H2O2, the secreted molecules appeared on the cell surface, and the Young's modulus was decreased significantly. However, PDA@CeO2 NPs could effectively inhibit the reduction of the Young's modulus caused by oxidative stress damage. PDA@CeO2 NPs could also protect F-actin from oxidative stress damage and maintain the stability of the cytoskeleton. This work investigates the intracellular antioxidant mechanism of nanomaterials from the changes in the microstructure and biomechanics of living cells, providing a new analytical approach to explore the biological effects of nanomaterials.
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Affiliation(s)
- Xinyue Guo
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. .,University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Zongjia Li
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. .,University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Sitong Liu
- The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, P. R. China.,School of Life Sciences, Jilin University, Changchun, 130012, P. R. China
| | - Miaomiao Zhang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
| | - Yanxue Guan
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. .,University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Juan Qin
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. .,University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Xiaomeng Li
- The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, P. R. China
| | - Bailin Zhang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. .,University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Jilin Tang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. .,University of Science and Technology of China, Hefei, 230026, P. R. China
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Mierke CT. The Pertinent Role of Cell and Matrix Mechanics in Cell Adhesion and Migration. Front Cell Dev Biol 2021; 9:720494. [PMID: 34722504 PMCID: PMC8548417 DOI: 10.3389/fcell.2021.720494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 09/20/2021] [Indexed: 01/17/2023] Open
Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, University of Leipzig, Leipzig, Germany
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41
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Tsitlakidis A, Tsingotjidou AS, Kritis A, Cheva A, Selviaridis P, Aifantis EC, Foroglou N. Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology. Cancers (Basel) 2021; 13:4539. [PMID: 34572766 PMCID: PMC8465072 DOI: 10.3390/cancers13184539] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/03/2021] [Accepted: 09/08/2021] [Indexed: 12/24/2022] Open
Abstract
This study aims to investigate the influence of isocitrate dehydrogenase gene family (IDH) mutations, World Health Organization (WHO) grade, and mechanical preconditioning on glioma and adjacent brain elasticity through standard monotonic and repetitive atomic force microscope (AFM) nanoindentation. The elastic modulus was measured ex vivo on fresh tissue specimens acquired during craniotomy from the tumor and the peritumoral white matter of 16 diffuse glioma patients. Linear mixed-effects models examined the impact of tumor traits and preconditioning on tissue elasticity. Tissues from IDH-mutant cases were stiffer than those from IDH-wildtype ones among anaplastic astrocytoma patients (p = 0.0496) but of similar elasticity to IDH-wildtype cases for diffuse astrocytoma patients (p = 0.480). The tumor was found to be non-significantly softer than white matter in anaplastic astrocytomas (p = 0.070), but of similar elasticity to adjacent brain in diffuse astrocytomas (p = 0.492) and glioblastomas (p = 0.593). During repetitive indentation, both tumor (p = 0.002) and white matter (p = 0.003) showed initial stiffening followed by softening. Stiffening was fully reversed in white matter (p = 0.942) and partially reversed in tumor (p = 0.015). Tissue elasticity comprises a phenotypic characteristic closely related to glioma histopathology. Heterogeneity between patients should be further explored.
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Affiliation(s)
- Abraham Tsitlakidis
- First Department of Neurosurgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (P.S.); (N.F.)
| | - Anastasia S. Tsingotjidou
- Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Aristeidis Kritis
- Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Angeliki Cheva
- Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Panagiotis Selviaridis
- First Department of Neurosurgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (P.S.); (N.F.)
| | - Elias C. Aifantis
- Laboratory of Mechanics and Materials, Polytechnic School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Nicolas Foroglou
- First Department of Neurosurgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (P.S.); (N.F.)
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Zhou H, Xue Y, Dong L, Wang C. Biomaterial-based physical regulation of macrophage behaviour. J Mater Chem B 2021; 9:3608-3621. [PMID: 33908577 DOI: 10.1039/d1tb00107h] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Macrophages play a critical role in regulating immune reactions induced by implanted biomaterials. They are highly plastic and in response to diverse stimuli in the microenvironment can exhibit a spectrum of phenotypes and functions. In addition to biochemical signals, the physical properties of biomaterials are becoming increasingly appreciated for their significant impact on macrophage behaviour, and the underlying mechanisms deserve more in-depth investigations. This review first summarises the effects of key physical cues - including stiffness, topography, physical confinement and applied force - on macrophage behaviour. Then, it reviews the current knowledge of cellular sensing and transduction of physical cues into intracellular signals. Finally, it discusses the major challenges in understanding mechanical regulation that could provide insights for biomaterial design.
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Affiliation(s)
- Huiqun Zhou
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.
| | - Yizebang Xue
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China. and Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Lei Dong
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School & School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China
| | - Chunming Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.
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43
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The Role of Peptide-Based Tumor Vaccines on Cytokines of Adaptive Immunity: A Review. Int J Pept Res Ther 2021. [DOI: 10.1007/s10989-021-10270-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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44
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Castro F, Leite Pereira C, Helena Macedo M, Almeida A, José Silveira M, Dias S, Patrícia Cardoso A, José Oliveira M, Sarmento B. Advances on colorectal cancer 3D models: The needed translational technology for nanomedicine screening. Adv Drug Deliv Rev 2021; 175:113824. [PMID: 34090966 DOI: 10.1016/j.addr.2021.06.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/23/2021] [Accepted: 06/01/2021] [Indexed: 02/08/2023]
Abstract
Colorectal cancer (CRC) is a heterogeneous and molecularly complex disease, associated with high mortality worldwide, exposing the urgent need for novel therapeutic approaches. Their development and translation to the clinic have been hampered, partially due to the absence of reliable cellular models that resemble key features of the human disease. While traditional 2D models are not able to provide consistent and predictive responses about the in vivo efficiency of the formulation, animal models frequently fail to recapitulate cancer progression and to reproduce adverse effects. On its turn, multicellular 3D systems, by mimicking key genetic, physical and mechanical cues of the tumor microenvironment, constitute a promising tool in cancer research. In addition, they constitute more physiological and relevant environment for anticancer drugs screening and for predicting patient's response towards personalized approaches, bridging the gap between simplified 2D models and unrepresentative animal models. In this review, we provide an overview of CRC 3D models for translational research, with focus on their potential for nanomedicines screening.
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45
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Peleg N, Schmilovitz-Weiss H, Shamah S, Schwartz A, Dotan I, Sapoznikov B. Neutrophil to lymphocyte ratio and risk of neoplastic progression in patients with Barrett's esophagus. Endoscopy 2021; 53:774-781. [PMID: 33075822 DOI: 10.1055/a-1292-8747] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Patient's with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). Neutrophil to lymphocyte ratio (NLR) was found to be a predictor of poor prognosis in patients with EAC; however, its performance in premalignant esophageal lesions is vague. We aimed to evaluate the utility of NLR as a predictor of histologic progression in patients with BE. METHODS : A prospective cohort of patients with proven BE in a tertiary referral center was retrospectively analyzed. All biopsies were reviewed by an expert gastrointestinal pathologist. The discriminatory capacity of NLR was evaluated by area under the receiver operating characteristic (AUC) curve analysis and Cox regression analysis. RESULTS 324 patients (mean age 62.3 years, 241 [74.4 %] males) were included in the final analysis. Overall, 13 patients demonstrated histologic progression to neoplasia over a mean follow-up of 3.7 years (progression risk 1.0 % per year). The AUC of NLR for progression to high grade dysplasia (HGD) or EAC was 0.88 (95 % confidence interval [CI] 0.83 - 0.96), and baseline NLR was associated with a 3-fold increase of progression to HGD and EAC during follow-up (hazard ratio [HR] 3.2, 95 %CI 1.5 - 5.8; P < 0.001). Notably, in a subgroup analysis of patients with nondysplastic BE (NDBE) at presentation, NLR was also a risk factor for histologic progression (HR 2.4, 95 %CI 1.7 - 3.4; P < 0.001). CONCLUSION NLR predicted histologic progression in patients with BE. Patients with NDBE and NLR above 2.4 can be considered for specific surveillance programs with shorter intervals between sessions.
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Affiliation(s)
- Noam Peleg
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hemda Schmilovitz-Weiss
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Steven Shamah
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ariel Schwartz
- Department of Pathology, Rabin Medical Center, Petah-Tikva, Israel
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Boris Sapoznikov
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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46
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Hou X, Tang L, Li X, Xiong F, Mo Y, Jiang X, Deng X, Peng M, Wu P, Zhao M, Ouyang J, Shi L, He Y, Yan Q, Zhang S, Gong Z, Li G, Zeng Z, Wang F, Guo C, Xiong W. Potassium Channel Protein KCNK6 Promotes Breast Cancer Cell Proliferation, Invasion, and Migration. Front Cell Dev Biol 2021; 9:616784. [PMID: 34195184 PMCID: PMC8237943 DOI: 10.3389/fcell.2021.616784] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 03/31/2021] [Indexed: 01/18/2023] Open
Abstract
Breast cancer is the most common malignant tumor in women, and its incidence is increasing each year. To effectively treat breast cancer, it is important to identify genes involved in its occurrence and development and to exploit them as potential drug therapy targets. Here, we found that potassium channel subfamily K member 6 (KCNK6) is significantly overexpressed in breast cancer, however, its function in tumors has not been reported. We further verified that KCNK6 expression is upregulated in breast cancer biopsies. Moreover, overexpressed KCNK6 was found to enhance the proliferation, invasion, and migration ability of breast cancer cells. These effects may occur by weakening cell adhesion and reducing cell hardness, thus affecting the malignant phenotype of breast cancer cells. Our study confirmed, for the first time, that increased KCNK6 expression in breast cancer cells may promote their proliferation, invasion, and migration. Moreover, considering that ion channels serve as therapeutic targets for many small molecular drugs in clinical treatment, targeting KCNK6 may represent a novel strategy for breast cancer therapies. Hence, the results of this study provide a theoretical basis for KCNK6 to become a potential molecular target for breast cancer treatment in the future.
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Affiliation(s)
- Xiangchan Hou
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Le Tang
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Xiayu Li
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Fang Xiong
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Yongzhen Mo
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Xianjie Jiang
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Xiangying Deng
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Miao Peng
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Pan Wu
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Mengyao Zhao
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Jiawei Ouyang
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Lei Shi
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yi He
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Qijia Yan
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Shanshan Zhang
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhaojian Gong
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Guiyuan Li
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Zhaoyang Zeng
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Fuyan Wang
- Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Can Guo
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, China
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A Universal Model for the Log-Normal Distribution of Elasticity in Polymeric Gels and Its Relevance to Mechanical Signature of Biological Tissues. BIOLOGY 2021; 10:biology10010064. [PMID: 33477413 PMCID: PMC7830536 DOI: 10.3390/biology10010064] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/08/2021] [Accepted: 01/15/2021] [Indexed: 01/19/2023]
Abstract
Simple Summary Mechanical properties of biological tissues are increasingly recognized as important in biology. Atomic force microscopy (AFM) is one of the main tools used to assess elastic properties of various types of biological samples. It has been noted that elasticity values frequently follow a log-normal distribution. We propose in this communication a physical model explaining this fact, and we propose that distribution-type analysis could increase the information obtained from AFM studies on biological tissues. Abstract The mechanosensitivity of cells has recently been identified as a process that could greatly influence a cell’s fate. To understand the interaction between cells and their surrounding extracellular matrix, the characterization of the mechanical properties of natural polymeric gels is needed. Atomic force microscopy (AFM) is one of the leading tools used to characterize mechanically biological tissues. It appears that the elasticity (elastic modulus) values obtained by AFM presents a log-normal distribution. Despite its ubiquity, the log-normal distribution concerning the elastic modulus of biological tissues does not have a clear explanation. In this paper, we propose a physical mechanism based on the weak universality of critical exponents in the percolation process leading to gelation. Following this, we discuss the relevance of this model for mechanical signatures of biological tissues.
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Boerner P, Nevozhay D, Hatamimoslehabadi M, Chawla HS, Zvietcovich F, Aglyamov S, Larin KV, Sokolov KV. Repetitive optical coherence elastography measurements with blinking nanobombs. BIOMEDICAL OPTICS EXPRESS 2020; 11:6659-6673. [PMID: 33282515 PMCID: PMC7687956 DOI: 10.1364/boe.401734] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 09/19/2020] [Accepted: 10/06/2020] [Indexed: 05/04/2023]
Abstract
Excitation of dye-loaded perfluorocarbon nanoparticles (nanobombs) can generate highly localized axially propagating longitudinal shear waves (LSW) that can be used to quantify tissue mechanical properties without transversal scanning of the imaging beam. In this study, we used repetitive excitations of dodecafluoropentane (C5) and tetradecafluorohexane (C6) nanobombs by a nanosecond-pulsed laser to produce multiple LSWs from a single spot in a phantom. A 1.5 MHz Fourier-domain mode-locked laser in combination with a phase correction algorithm was used to perform elastography. Multiple nanobomb activations were also monitored by detecting photoacoustic signals. Our results demonstrate that C6 nanobombs can be used for repetitive generation of LSW from a single spot for the purpose of material elasticity assessment. This study opens new avenues for continuous quantification of tissue mechanical properties using single delivery of the nanoparticles.
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Affiliation(s)
- Paul Boerner
- Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA
- Equal contribution
| | - Dmitry Nevozhay
- Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
- Equal contribution
| | | | | | - Fernando Zvietcovich
- Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA
| | - Salavat Aglyamov
- Department of Mechanical Engineering, University of Houston, Houston, Texas 77204, USA
| | - Kirill V Larin
- Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA
| | - Konstantin V Sokolov
- Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
- Department of Bioengineering, Rice University, Houston, Texas 77030, USA
- Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton Street, Austin, Texas 78712, USA
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Ataca Atilla P, McKenna MK, Tashiro H, Srinivasan M, Mo F, Watanabe N, Simons BW, McLean Stevens A, Redell MS, Heslop HE, Mamonkin M, Brenner MK, Atilla E. Modulating TNFα activity allows transgenic IL15-Expressing CLL-1 CAR T cells to safely eliminate acute myeloid leukemia. J Immunother Cancer 2020; 8:jitc-2020-001229. [PMID: 32938629 PMCID: PMC7497527 DOI: 10.1136/jitc-2020-001229] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/04/2020] [Indexed: 12/12/2022] Open
Abstract
Background C-type lectin-like molecule 1 (CLL-1) is highly expressed in acute myeloid leukemia (AML) but is absent in primitive hematopoietic progenitors, making it an attractive target for a chimeric antigen receptor (CAR) T-cell therapy. Here, we optimized our CLL-1 CAR for anti-leukemic activity in mouse xenograft models of aggressive AML. Methods First, we optimized the CLL-1 CAR using different spacer, transmembrane and costimulatory sequences. We used a second retroviral vector to coexpress transgenic IL15. We measured the effects of each construct on T cell phenotype and sequential (recursive) co culture assays with tumor cell targets to determine the durability of the anti tumor activity by flow cytometry. We administered CAR T cells to mice engrafted with patient derived xenografts (PDX) and AML cell line and determined anti tumor activity by bioluminescence imaging and weekly bleeding, measured serum cytokines by multiplex analysis. After euthanasia, we examined formalin-fixed/paraffin embedded sections. Unpaired two-tailed Student’s t-tests were used and values of p<0.05 were considered significant. Survival was calculated using Mantel-Cox log-rank test. Results In vitro, CLL-1 CAR T cells with interleukin-15 (IL15) were less terminally differentiated (p<0.0001) and had superior expansion compared with CD28z-CD8 CAR T cells without IL15 (p<0.001). In both AML PDX and AML cell line animal models, CLL-1 CAR T coexpressing transgenic IL15 initially expanded better than CD28z-CD8 CAR T without IL15 (p<0.0001), but produced severe acute toxicity associated with high level production of human tumor necrosis factor α (TNFα), IL15 and IL2. Histopathology showed marked inflammatory changes with tissue damage in lung and liver. This acute toxicity could be managed by two strategies, individually or in combination. The excessive TNF alpha secretion could be blocked with anti-TNF alpha antibody, while excessive T cell expansion could be arrested by activation of an inducible caspase nine safety switch by administration of dimerizing drug. Both strategies successfully prolonged tumor-free survival. Conclusion Combinatorial treatment with a TNFα blocking antibody and subsequent activation of the caspase-9 control switch increased the expansion, survival and antileukemic potency of CLL-1 CAR T-cells expressing transgenic IL15 while avoiding the toxicities associated with excessive cytokine production and long-term accumulation of activated T-cells.
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Affiliation(s)
- Pinar Ataca Atilla
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
| | - Mary K McKenna
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
| | - Haruko Tashiro
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
| | | | - Feiyan Mo
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
| | - Norihiro Watanabe
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
| | - Brian Wesley Simons
- Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Alexandra McLean Stevens
- Division of Pediatric Hematology/Oncology, Texas Children's Hospital, Houston, Texas, USA.,Division of Pediatric Hematology/Oncology, Baylor College of Medicine, Houston, Texas, USA
| | - Michele S Redell
- Division of Pediatric Hematology/Oncology, Texas Children's Hospital, Houston, Texas, USA.,Division of Pediatric Hematology/Oncology, Baylor College of Medicine, Houston, Texas, USA
| | - Helen E Heslop
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.,Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas, USA.,Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.,Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Maksim Mamonkin
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.,Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
| | - Malcolm K Brenner
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.,Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas, USA.,Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.,Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Erden Atilla
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
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Aermes C, Hayn A, Fischer T, Mierke CT. Environmentally controlled magnetic nano-tweezer for living cells and extracellular matrices. Sci Rep 2020; 10:13453. [PMID: 32778758 PMCID: PMC7417586 DOI: 10.1038/s41598-020-70428-w] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 07/16/2020] [Indexed: 01/08/2023] Open
Abstract
The magnetic tweezer technique has become a versatile tool for unfolding or folding of individual molecules, mainly DNA. In addition to single molecule analysis, the magnetic tweezer can be used to analyze the mechanical properties of cells and extracellular matrices. We have established a magnetic tweezer that is capable of measuring the linear and non-linear viscoelastic behavior of a wide range of soft matter in precisely controlled environmental conditions, such as temperature, CO2 and humidity. The magnetic tweezer presented in this study is suitable to detect specific differences in the mechanical properties of different cell lines, such as human breast cancer cells and mouse embryonic fibroblasts, as well as collagen matrices of distinct concentrations in the presence and absence of fibronectin crosslinks. The precise calibration and control mechanism employed in the presented magnetic tweezer setup provides the ability to apply physiological force up to 5 nN on 4.5 µm superparamagnetic beads coated with fibronectin and coupled to the cells or collagen matrices. These measurements reveal specific local linear and non-linear viscoelastic behavior of the investigated samples. The viscoelastic response of cells and collagen matrices to the force application is best described by a weak power law behavior. Our results demonstrate that the stress stiffening response and the fluidization of cells is cell type specific and varies largely between differently invasive and aggressive cancer cells. Finally, we showed that the viscoelastic behavior of collagen matrices with and without fibronectin crosslinks measured by the magnetic tweezer can be related to the microstructure of these matrices.
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Affiliation(s)
- Christian Aermes
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, University of Leipzig, Linnéstr. 5, 04103, Leipzig, Germany
| | - Alexander Hayn
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, University of Leipzig, Linnéstr. 5, 04103, Leipzig, Germany
| | - Tony Fischer
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, University of Leipzig, Linnéstr. 5, 04103, Leipzig, Germany
| | - Claudia Tanja Mierke
- Faculty of Physics and Earth Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, University of Leipzig, Linnéstr. 5, 04103, Leipzig, Germany.
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