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Hemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular oxidative level.

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Ma S,Fu A,Chiew GG,Luo KQ

doi

10.1016/j.canlet.2016.12.001

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

239-248

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(16)30746-7

journal_volume

388

pub_type

杂志文章

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