Compression‐induced cell distension stimulates coordinated migration of mammary carcinoma cells

Abstract

Uncontrolled cell proliferation of a solid tumor in a confined space not only creates oxidative stress (hypoxia), but also generates mechanical compressive stress, which can influence the tumor cells and modify their interactions with neighboring cells and the extracellular matrix. Little is known about how such compressive stress affects cancer progression. Here we show, for the first time, that externally‐applied compressive stress results in faster migration of mammary carcinoma cells. Compression induces migration of mammary carcinoma cells in a coordinated sheet, initiated by “leader cells” – single cells at the leading edge of the sheet, extending long filopodia. Accompanied by redistribution of fibronectin deposition, applied compression enhances cell‐matrix adhesion and stabilizes cell distension independent of actomyosin contractile machinery. Our results suggest that mechanical stress accumulated during tumor growth is sufficient to enhance cell‐substrate adhesion and stimulate cancer cell migration. This mechanism opens the door to a new class of targets for blocking mechanical stress pathways. Funding for this work was provided by NIH grant R01CA085140.

Extracellular Mechanical Stimuli Alters the Metastatic Progression of Prostate Cancer Cells within 3D Tissue Matrix

“…All mechanical loading conditions utilized in this study are physiologically relevant. Bone mechanotransduction studies report that moderate activities (i.e., walking) create lower amplitude of mechanical stimuli within the bone with low frequencies (<2 Hz) thousands of times with an amplitude of 1% strain [33,[36][37][38][39][40]. This study's cyclic mechanical stimuli applied with 1% strain at 1 Hz represent the mechanical loading on the bone microenvironment due to physical activities.…”