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

• Published in: PloS one Vol. 7; no. 12; p. e50973
• Main Authors: Barnes, J Matthew, Nauseef, Jones T, Henry, Michael D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.12.2012; Public Library of Science (PLoS)
• Subjects: Actin; Actins; Biochemistry; Biology; Biomechanical Phenomena; Biophysical Phenomena; Biophysics; Blood; Calcium; Calcium (extracellular); Calcium - metabolism; Calcium signalling; Cancer; Cancer metastasis; Cell adhesion & migration; Cell Death; Cell Line, Tumor; Cell Membrane - metabolism; Cell Survival; Cell Transformation, Neoplastic; Cells (Biology); Colorectal cancer; Cytoskeleton; Endothelium; Epithelial cells; Extracellular matrix; Extracellular Space - metabolism; Fluid flow; Gene expression; Hemodynamics; Humans; Kinases; Mechanical stimuli; Medical research; Medicine; Melanoma; Metastases; Metastasis; Microfluidics; Models, Biological; Neoplasms - metabolism; Neoplasms - pathology; Oncogenes - genetics; Physics; Physiology; Polymerization; Prostate; Rheology; Shear resistance; Shear strength; Shear stress; Shear stresses; Stress, Mechanical; Studies; Tissues; Transformed cells; Viability; United States > US; Iowa City Iowa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0050973

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. 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 FSS. We show that magnitude of FSS resistance is influenced by several oncogenes, is an adaptive and transient response triggered by plasma membrane damage and requires extracellular calcium and actin cytoskeletal dynamics. 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.