UC San Diego

Cell migration is thought to be driven by interactions with the surrounding environment. Utilizing the core four biophysical features including adhesion, contractility, degradation, and actin cytoskeletal polymerization, cells interrogate their environment and use sensory feedback to promote proliferation or migration. Collagen I, an essential component of the stroma has been implicated in inducing migratory behavior in both normal and cancer cells, suggesting that the microenvironment plays a key role in directing cell fate. Additionally, matrix tension is thought to be a promoter of contractile force generation and invasion in normal cells. Recent studies were able to induce invasive behavior in MCF10A normal mammary epithelial cells by implanting them in a collagen I rich environment. However, release of matrix tension promoted conversion of cells to a non-invasive phenotype. Since we’ve demonstrated persistent collective invasion of MDA-MB-231 cancer cells is promoted in low attachment environments, I hypothesized that cancer cells would be less sensitive to the effect of matrix tension release. Comparison of tension release in normal cells vs cancer cells demonstrated significant, but less distinctive shift in distribution towards the non-invasive spheroid phenotype in cancer. Uniquely, low matrix tension conditions promoted proliferation in structures independent of invasiveness. Additionally, invasive network phenotypes acquired pseudo-normal morphology including capacity for lumen formation. Investigation of potential cell-ECM and cell-cell interaction driving this behavior suggested that increased cell-cell adhesion and contractility induced intercellular tension regulates invasive behavior and may stimulate proliferation increases. Finally, calcium mediated adhesion was found to play an important role in structure stability.