One of the rate limiting steps in the progression of cancer is the acquisition of angiogenicity. In fact, the induction of angiogenesis not only allows the primary tumor to grow beyond the size limitation of 2mm, imposed by the diffusion limit of oxygen, but also provides a conduit through which the tumors can travel to and colonize distant organs. Once the tumor cells arrive at the metastatic site they must also induce neovascualarization in order to grow beyond the 2mm size constraint. Often, however, the metastasis remains dormant and does not progress beyond this size for months or years following its colonization.
The role of the tumor-associated stroma has been demonstrated to be of significant importance to both breast and prostate cancer formation, perhaps moreso than in other cancers. It has been demonstrated, for instance, that stromal fibroblasts isolated from a prostate tumor induce tumor formation of immortal but non-transformed prostate epithelial cells when the mixture is injected orthotopically into nude mice. Thus it would appear that prostate cancer cells have a strong dependence on their surrounding stroma. More importantly, prostate cancer cells are able to alter their surrounding stromal fibroblasts to enhance tumor growth. As such, we study the regulation of angiogenesis, proliferation and motility in both epithelial cells and fibroblasts. We have identified a novel suppressor of metastasis, Prosaposin, which acts both locally and distally by stimulating the expression/activity of p53, which then stimulates the expression of Tsp-1. Significantly, Prosaposin also inhibits metastasis when administered in a systemic fashion thus making it a potential therapeutic agent to stem the metastatic dissemination of human tumors.
About Randolph Watnick
Dr. Watnick received his Bachelor of Science degree from Trinity College, in Hartford, CT, in 1993. He went on to earn a Ph.D. in Biochemistry and Molecular Biophysics from Columbia University in 1999. At Columbia, Dr. Watnick received a pre-doctoral fellowship from the National Eye Institute and was awarded the Samuel and Lewis Rover Award for outstanding research in Biochemistry and Molecular Biophysics. After receiving his Ph.D., Dr. Watnick continued his training as a post-doctoral fellow in the laboratory of Dr. Robert Weinberg at the Whitehead Institute for Biomedical Research. During this time Dr. Watnick was awarded a Damon Runyon post-doctoral fellowship. In 2003 Dr. Watnick was appointed an Assistant Professor in the Department of Surgery at Harvard Medical School and a Research Associate in the Vascular Biology Program at Boston Children's Hospital.