(147e) Fluid Shear Stress Activates Epithelial-to-Mesenchymal Transition Genes in Luminal Breast Cancer Subtype

Metastasis is the leading cause of cancer deaths due to the spread of cancer cells through the blood vessels leading to the formation of secondary tumors. Metastasizing cancer cells in the human vasculature are called circulating tumor cells (CTCs) and are characterized to express epithelial cell adhesion molecule (EpCAM). They are further known to survive the harsh physiological fluid shear stress (FSS) conditions. However, the effect of FSS on CTC molecular phenotype, such as the epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) expression, has not been extensively studied. Here, we created an in vitro model system using COMSOL Multiphysics and a syringe pump for experimental FSS to evaluate CTCs in blood flow. Breast epithelial cell line 184A1 and breast cancer cell lines MCF7, SKBR3, and MDA-MB-231 were tested for cell viability. Gene expression and CSC expression were tested on the MCF7 and MDA-MB-231 cell lines. Results show that cell viability under FSS is variable in different breast cancer cell types with breast cancer cells having a higher viability under fluid shear stress compared to the 184A1 cell line. The difference in breast cancer cell type also correlated to differences in epithelial and mesenchymal gene expression with the more invasive MDA-MB-231 having higher mesenchymal gene expression. Upon application of FSS, there was an upregulation of genes in MCF7 cells and MDA-MB-231 cells. However, cancer stem cell expression which is seen in metastatic cancer cells was more resistant to expression changes under fluid shear stress. These results show that the luminal breast cancer subtype is more susceptible to the effects of FSS with greater changes in their genetic and protein expression.