Tumorigenesis and metastasis depend upon a complex series of events, and it is believed that cell attachment plays a critical role in those processes. The applicants have developed a polymeric form of the cell adhesion molecule fibronectin and have shown that this agent, referred to as superfibronectin (sFN), inhibits cell attachment, as well as cell migration in vitro. In vivo, sFN has anti-metastatic activity towards several human tumors inoculated in immunodeficient mice. Preliminary studies with ovarian carcinoma cell lines have shown that sFN can restrict the growth and the peritoneal spread of injected tumor cells. There have been no discernible toxic effects from the sFN treatment. The applicants propose to: 1) test , as an initial step toward designing clinical trials, the therapeutic effect of sFN in an ovarian cancer animal model that mimics the human disease. 2) to assess sFN toxicity focusing on the histological analysis of multiple organs from animals treated with escalating doses of the polymer and 3) to develop a light scattering test to standardize the production of the sFN polymer. These studies are expected to provide the information needed to proceed into experimental clinical trials after the phase II of this grant.
