title: Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells.
abstract: 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.
authors.affiliation: Microsystems Engineering, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Mechanical Engineering, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Emery
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Applied Physics and Applied Mathematics/Materials Science and Engineering Program, Columbia University, New York, USA.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Microsystems Engineering, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Jiandi
authors.initials: J
authors.lastname: Wan
mesh_terms: D001696:Biomechanical Phenomena; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival; D015870:Gene Expression; D045325:HCT116 Cells; D006801:Humans; D040542:Mechanotransduction, Cellular; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D008954:Models, Biological; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012212:Rheology; D013314:Stress, Mechanical; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin