Rick Cerione, Project Leader
Focus on a key outcome of cancer cell metabolism: the generation of microvesicles (MVs), which are shed from the plasma membranes of cancer cells. MVs have been implicated in the metastatic process by changing the tumor microenvironment and stimulating tumor angiogenesis. Although we understand some of the biochemical signals triggering MV production, we know little about the physical determinants driving their formation, or how the physical microenvironment influences their biogenesis and function. We will probe these issues as follows: 1) Determine the physical relationships governing MV biogenesis and size distribution; 2) determine the reciprocal relationship between the physical properties of the extracellular matrix and MV formation; 3) establish physical read-outs such as vesicle size as indicators of MV function in tumor-stroma and reciprocal stroma-tumor vesicle transfer. These studies should shed new light on how cancer cell metabolism stimulates MV biogenesis, and ultimately lead to novel therapeutic strategies.