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Metastatic ovarian cancer cell malignancy is increased on soft matrices through a mechanosensitive Rho/ROCK pathway
Daniel J. McGrail, Quang Minh N. Kieu, Michelle R. Dawson


Though current treatments for localized ovarian cancer are highly effective, it still remains the most lethal gynecological malignancy, largely in part to late detection after tumor cells leave the primary tumor. Clinicians have long noted a clear predilection for ovarian cancer metastasis to the soft omentum. Here, we show that this tropism is due not only to chemical signals but also mechanical cues. Metastatic ovarian cancer cells (OCCs) preferentially adhere to soft microenvironments and display an enhanced malignant phenotype including increased migration, proliferation, and chemoresistance. To understand the cell-matrix interactions used to sense the substrate rigidity, we utilized traction force microscopy and found that OCCs increased both the magnitude of traction forces as well as their degree of polarization. After culture on soft substrates, cells underwent morphological elongation characteristic of epithelial-mesenchymal transition, which was confirmed by molecular analysis. Consistent with the idea that mechanical cues are a key determinant in the spread of ovarian cancer, the observed mechanosensitivity was greatly decreased in less metastatic OCCs. Finally, we demonstrate that this mechanical tropism is governed through a Rho/ROCK signaling pathway.