Many of the hallmarks associated with cancer, including unlimited replicative potential, apoptotic evasion, and tissue invasion and metastasis, can be linked to abnormal cytoskeletal or matrix mechanics – important biophysical parameters. A common feature of these biophysical interactions is the transmission of force from the extracellular matrix to the internal cytoskeleton, which forms the structure of the cell. My lab recently showed that increased traction forces transmitted from the internal cytoskeleton to the external environment correlate with increased cancer cell motility, proliferation, and chemoresistance; this was demonstrated in mechanosensitive breast and ovarian cancer cells that respond to changes in matrix stiffness and in a genetic model of induced epithelial to mesenchymal transition. We also showed that paracrine factors exchanged between cancer and stromal cells dramatically alter the mechanical properties of both cell types. Mechanical forces in the primary tumor are caused by solid stress that results from the rapid proliferation of tumor cells and the recruitment of host-derived stromal cells. Matrix stiffening and high-interstitial fluid pressure further contribute to this high stress environment, which alters cells and the surrounding matrix to activate signaling pathways important in cancer. Mechanical forces are also critical in directing cancer metastasis. In fact, cancer cells undergo a cascade of biophysical changes throughout this process. Quantitative analysis of intracellular mechanics, surface traction forces, and matrix stiffness allows us to probe the biomechanical properties of the tumor with an unprecedented level of detail. These biophysical techniques can be used to systematically investigate the parameters in the tumor that control cancer cell interactions with the stroma and to identify specific conditions that induce tumor-promoting behavior, along with strategies for inhibiting these conditions to treat cancer. My presentation will focus on lessons we’ve learned through quantitative biophysical analysis of cells in the tumor microenvironment I will also discuss current research projects focused on investigating the role of stromal cell aging in cancer progression and mechanisms contributing to chemotherapy and radiation resistance
