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Volume 2, Issue 2 (Suppl) Breast Can Curr Res
ISSN: 2572-4118 BCCR, an open access journal Breast Cancer Summit 2017
May 08-10, 2017
May 08-10, 2017 Singapore
4th World Congress on
Breast Cancer
Hemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular
oxidative stress
Shijun Ma1 , Kathy Qian Luo2
1Nanyang Technological University, Singapore
2University of Macau, China
C irculation of cancer cells in blood flow is an important phase for distant cancer metastasis, during which cancer cells are exposed
to hemodynamic shear stress. Recent studies identified shear stress as the primary factor that damages circulating tumor cells in
blood flow. However, it remains unclear whether shear stress can modulate properties and functions of tumor cells in a manner that
might help tumor cells to exit circulation. In our study, we demonstrate that fluidic shear stress could positively regulate migration
and extravasation of surviving tumor cells in circulation, and facilitate metastasis. We established a microfluidic circulatory system
to apply physiological fluidic shear stress on breast cancer cells and mimic the physical environment in blood flow. An arterial
level of shear stress generated in the circulatory system significantly increased tumor cell migration in both transwell and wound
healing assays. We also observed that shear stress enhanced extravasation of breast tumor cells in a transendothelial assay. The
mechanistic study identified the elevation of cellular ROS as an early molecular event induced by shear stress. The excessive cellular
ROS subsequently activates ERK1/2 pathway, which leads to tumor cell migration and extravasation. Finally, by using a zebrafish
model, we demonstrated that application of antioxidants could suppress shear stress-enhanced tumor cell extravasation in vivo. This
new understanding of how fluidic shear stress promotes metastatic potential of tumor cells has important implications in cancer
treatment and can help us identify latent therapeutic targets for inhibiting tumor progression.
Biography
Ma Shijun received his BS from Wuhan University in China. He is currently a PhD candidate in School of Chemical and Biomedical Engineering, Nanyang
Technological University. His current research work focuses on the how hemodynamic shear stress influences tumor cell migration and adhesion.
Shijun Ma et al., Breast Can Curr Res 2017, 2:2(Suppl)