کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525691 1546681 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleHemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular oxidative level
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleHemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular oxidative level
چکیده انگلیسی


- This is the first report on the pro-metastatic effect of shear stress on tumor cells.
- Fluid shear stress promotes the migration and extravasation of tumor cells.
- Fluid shear stress confers this effect by generating ROS which then activates ERK1/2.
- Antioxidants suppress the migration and extravasation of tumor cells in zebrafish model.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 388, 1 March 2017, Pages 239-248
نویسندگان
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