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Title: Hemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular oxidative level
Authors: Ma, Shijun
Fu, Afu
Chiew, Geraldine Giap Ying
Luo, Kathy Qian
Keywords: Circulating tumor cells
Shear stress
Issue Date: 2017
Source: Ma, S., Fu, A., Chiew, G. G. Y., & Luo, K. Q. (2017). Hemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular oxidative level. Cancer Letters, 388, 239-248.
Series/Report no.: Cancer Letters
Abstract: Cancer cells are shed into the blood stream and are exposed to hemodynamic shear stress during metastasis. It has been shown that shear stress can destroy circulating tumor cells (CTCs) both in vitro and in vivo. However, it remains unclear whether shear stress can modulate the properties and functions of tumor cells in a manner that might help CTCs to exit circulation. In this study, we established a microfluidic circulatory system to apply physiological fluid shear stress on breast cancer cells and demonstrated that an arterial level of shear stress significantly enhanced tumor cell migration in transwell and wound healing assays, and enhanced extravasation in a transendothelial assay. Circulatory treatment elevated the intracellular levels of reactive oxygen species (ROS), which is an early and indispensable event for activating the extracellular signal-regulated kinases (ERK1/2). Subsequently, ERK1/2 activation promoted the migration of tumor cells and enhanced their extravasation. Finally, reducing cellular ROS production suppressed tumor cell extravasation in both a transendothelial assay and a zebrafish model. This new understanding of how fluid shear stress promotes tumor cell migration has important implications in cancer treatment and can help us to identify potential therapeutic targets for inhibiting tumor progression.
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2016.12.001
Schools: School of Chemical and Biomedical Engineering 
Rights: © 2016 Elsevier Ireland Ltd. This is the author created version of a work that has been peer reviewed and accepted for publication by Cancer Letters, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCBE Journal Articles

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