Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells
Open accessAbstract
During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm 2), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of β-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis.
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Techniques that overcome abnormal vasculature in the tumor, such as nanoparticle drug delivery and drugs normalizing vascular network, were shown to be able to greatly improve anti-cancer treatment.
“In recent years, techniques which can overcome the abnormal vasculature in the tumor, such as nanoparticle drug delivery and drugs normalizing vascular network, were shown to be able to greatly improve anti-cancer treatment [108-113].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [113]
The Abstract and Discussion describe how circulatory shear stress affects colon cancer cell viability and proliferation, not treatments that overcome abnormal tumor vasculature. Searches for nanoparticle drug delivery and vascular normalization found no passage addressing whether those techniques improve anti-cancer treatment; no page numbers are available in our copy. (LLM, conf=0.75)
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References 37 · Cited by 103
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- Chaffer C. L. & Weinberg R. A. A perspective on cancer cell metastasis. Science 331, 1559– 1564 (2011). 21436443
- Jemal A.. Cancer statistics, 2008. CA: Cancer J. Clin. 58, 71– 96 (2008). 18287387
- Chivukula V. K., Krog B. L., Nauseef J. T., Henry M. D. & Vigmostad S. C. Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study. Cell Health Cytoskelet 7, 25 (2015). 25908902 PMC4405123
- Gupta G. P. & Massagué J. Cancer metastasis: building a framework. Cell 127, 679– 695 (2006). 17110329
- Wirtz D., Konstantopoulos K. & Searson P. C. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11, 512– 522 (2011). 21701513 PMC3262453
- Porquet N.. Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3. BMC cancer 11, 285 (2011). 21722370 PMC3177907
- Luo C.-W., Wu C.-C. & Ch’ang H.-J. Radiation sensitization of tumor cells induced by shear stress: The roles of integrins and FAK. BBA-Mol. Cell Res. 1843, 2129– 2137 (2014). 24946134
- Ziółkowska K.. Long-term three-dimensional cell culture and anticancer drug activity evaluation in a microfluidic chip. Biosens. Bioelectron 40, 68– 74 (2013). 22770829
- Mitchell M. J. & King M. R. Fluid shear stress sensitizes cancer cells to receptor-mediated apoptosis via trimeric death receptors. New J. Phys. 15, 015008 (2013). PMC4124740 25110459
- Jadhav S., Bochner B. S. & Konstantopoulos K. Hydrodynamic shear regulates the kinetics and receptor specificity of polymorphonuclear leukocyte-colon carcinoma cell adhesive interactions. J. Immunol 167, 5986– 5993 (2001). 11698478
- Thamilselvan V., Patel A., Voort van Zyp J. v. d. & Basson M. D. Colon cancer cell adhesion in response to Src kinase activation and actin‐cytoskeleton by non‐laminar shear stress. J. Cell. Biochem 92, 361– 371 (2004). 15108361
- Nagrath S.. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235– 1239 (2007). 18097410 PMC3090667
- Turitto V. Blood viscosity, mass transport, and thrombogenesis. Prog Hemost Thromb 6, 139– 177 (1981). 6762611
- Lyczkowski R. W., Alevriadou B. R., Horner M., Panchal C. B. & Shroff S. G. Application of multiphase computational fluid dynamics to analyze monocyte adhesion. Ann. Biomed. Eng. 37, 1516– 1533 (2009). 19521774
- Duan Y.. β-Catenin activity negatively regulates bacteria-induced inflammation. Lab. Invest 87, 613– 624 (2007). 17384665
- Hashimoto S.. Role of p53 in human chondrocyte apoptosis in response to shear strain. Arthritis Rheumatol. 60, 2340– 2349 (2009). 19644890
- Zhong J. J., Fujiyama K., Seki T. & Yoshida T. A quantitative analysis of shear effects on cell suspension and cell culture of Perilla frutescens in bioreactors. Biotechnol. Bioeng. 44, 649– 654 (1994). 18618801
- Abu-Reesh I. & Kargi F. Biological responses of hybridoma cells to defined hydrodynamic shear stress. J. Biotechnol. 9, 167– 178 (1989). 1368002
- Morin P. J. β-catenin signaling and cancer. Bioessays 21, 1021– 1030 (1999). 10580987
- Hintermann E., Bilban M., Sharabi A. & Quaranta V. Inhibitory role of α6β4-associated erbB-2 and phosphoinositide 3-kinase in keratinocyte haptotactic migration dependent on α3β1 integrin. J. Cell Biol. 153, 465– 478 (2001). 11331299 PMC2190561
- Shaw L. M., Rabinovitz I., Wang H. H.-F., Toker A. & Mercurio A. M. Activation of phosphoinositide 3-OH kinase by the α6β4 integrin promotes carcinoma invasion. Cell 91, 949– 960 (1997). 9428518
- Rousseau S., Houle F., Landry J. & Huot J. p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene 15, 2169– 2177 (1997). 9393975
- Mao B.. Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling. Nature 417, 664– 667 (2002). 12050670
- Hildesheim J.. Gadd45a regulates matrix metalloproteinases by suppressing ΔNp63α and β-catenin via p38 MAP kinase and APC complex activation. Oncogene 23, 1829– 1837 (2004). 14647429
- Bachelder R. E., Marchetti A., Falcioni R., Soddu S. & Mercurio A. M. Activation of p53 function in carcinoma cells by the α6β4 integrin. J. Biol. Chem. 274, 20733– 20737 (1999). 10400708
- Resnick N.. Fluid shear stress and the vascular endothelium: for better and for worse. Prog. Biophys. Mol. Biol. 81, 177– 199 (2003). 12732261
- Yoshisue H.. Large scale isolation of non-uniform shear stress-responsive genes from cultured human endothelial cells through the preparation of a subtracted cDNA library. Atherosclerosis 162, 323– 334 (2002). 11996952
- Li Y.-S. J., Haga J. H. & Chien S. Molecular basis of the effects of shear stress on vascular endothelial cells. J. Biomech 38, 1949– 1971 (2005). 16084198
- Kamel M. A., Picconi J. L., Lara-Castillo N. & Johnson M. L. Activation of β-catenin signaling in MLO-Y4 osteocytic cells versus 2t3 osteoblastic cells by fluid flow shear stress and PGE 2: Implications for the study of mechanosensation in bone. Bone 47, 872– 881 (2010). 20713195 PMC2952691
- Noris M.. Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions. Circ. Res. 76, 536– 543 (1995). 7534657
- Bouskela E., Cyrino F. Z. & Marcelon G. Effects of Ruscus extract on the internal diameter of arterioles and venules of the hamster cheek pouch microcirculation. J. Cardiovasc. Pharmacol. 22, 221– 224 (1993). 7692161
- Authors
- Fan, R., Emery, T., Zhang, Y., Xia, Y., Sun, J., & Wan, J.
- Affiliations
- Rochester Institute of Technology (US)
- University of Illinois Chicago (US)
- Columbia University (US)
- Corresponding author
- Sun, Jun
- Wan, Jiandi
- Venue
- Scientific Reports
- Published
- 2016-06-03
- Volume
- 6
- Issue
- 1
- Pages
- 27073-27073
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4891768
- OpenAlex
- W2468954576
- Cited by
- 103
- References
- 37
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 11 · 2023: 12 · 2022: 14 · 2021: 15 · 2020: 11 · 2019: 16 · 2018: 11 · 2017: 3
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Swim Across America
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK105118)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Bio-sensing Technologies
- Keywords
- circulating tumor cells, colon cancer, wall shear stress, hemodynamic shear stress, cell viability, cell proliferation, metastasis, β-catenin, c-Myc, mechanosensing, HCT116 cells
- MeSH terms
- Biomechanical Phenomena, Cell Survival, Humans, Models, Biological, Neoplastic Cells, Circulating, Rheology, Stress, Mechanical, Gene Expression, Proto-Oncogene Proteins c-myc, Mechanotransduction, Cellular, HCT116 Cells, Microfluidic Analytical Techniques, Cell Proliferation, beta Catenin
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