Mechanical compression drives cancer cells toward invasive phenotype

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 3; pp. 911 - 916
• Main Authors: Tse, Janet M, Cheng, Gang, Tyrrell, James A, Wilcox-Adelman, Sarah A, Boucher, Yves, Jain, Rakesh K, Munn, Lance L
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.01.2012; National Acad Sciences
• Series: From the Cover
• Subjects: Actomyosin - metabolism; Adhesion; Biological Sciences; Breast Neoplasms - pathology; Cancer; carcinoma; Cell Adhesion; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell lines; Cell Movement; Cell-Matrix Junctions - metabolism; Compressive stress; Confined spaces; Cultured cells; Cytoskeleton - metabolism; Disease prevention; Endothelial cells; Epithelial cells; Female; Focal adhesions; Genotype & phenotype; Humans; Models, Biological; Neoplasm Invasiveness; Phenotype; Physical Sciences; Pseudopodia - metabolism; Stress, Mechanical; Tumors
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1118910109

Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of "leader cells" that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell microorganization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell–matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell–substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion.