Abstract C30: Resistance to fluid shear stress is a conserved biophysical property of malignant cells

Abstract

During metastasis, cancer cells enter the circulation in order to gain access to distant tissues, but how this fluid microenvironment influences cancer cell biology is poorly understood. A longstanding view is that circulating cancer cells derived from solid tissues may be susceptible to damage from hemodynamic shear forces, contributing to metastatic inefficiency. However, there have been few efforts to directly test this hypothesis. Here we report that compared to non-transformed epithelial cells, transformed cells are remarkably resistant to fluid shear stress (FSS) in a microfluidic protocol, exhibiting a biphasic decrease in viability when subjected to a series of millisecond pulses of high (750-6,300 dyn/cm²) FSS. We show that magnitude of FSS resistance is influenced by several oncogenes including myc, ras, and PI3K; is an adaptive and transient response triggered by reparable plasma membrane damage; and requires extracellular calcium and actin cytoskeletal dynamics, including the activity of Rho kinase. This novel property of malignant cancer cells may facilitate hematogenous metastasis and indicates, contrary to expectations, that cancer cells are quite resistant to destruction by hemodynamic shear forces.

Citation Format: James Matthew Barnes, Jones T. Nauseef, Michael D. Henry. Resistance to fluid shear stress is a conserved biophysical property of malignant cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C30.