Brief Pulses of High-Level Fluid Shear Stress Enhance Metastatic Potential and Rapidly Alter the Metabolism of Cancer Cells

Circulating tumor cells (CTCs) face challenges to their survival including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade are not well understood. Here we find that cancer cells (PC-3, MDA-MB-231, Myc-CaP) exposed to brief pulses of high-level FSS exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling and contractility as well as reducing equivalents to counter oxidative stress associated with cell detachment. Thus, exposure to FSS may provide CTCs an unexpected survival benefit that promotes metastatic colonization. Overall design: RNAsequeince of PC-3 that were either briefly exposed to fluid shear stress (sheared) or not (static) and then held in suspension for 3, 12, or 24 hours after exposure. Experiment was performed such that sheared and static samples for an individual biological replicate within a timepoint can be paired as they are from an original pool of cells. Data from between timepoints are biologically independent