Project Summary (2000-2005)

The goal of this project is to investigate the hypothesis that exposure to specific polychlorinated biphenyls (PCBs) enhances the risk for the development of tumor metastasis. The mechanisms of this process involve PCB-induced effects on adhesion molecule expression on the surface of vascular endothelial cells. This process may allow interaction between tumor cells and endothelial cells and thus facilitate migration of tumor cells across the endothelium and metastatic invasion of the surrounding tissues. One of the most important adhesion molecules involved in metastasis is the intercellular adhesion molecule (ICAM-1). The expression of this adhesion molecule on vascular endothelium is increased in most common human cancers. Preliminary data indicate that selected PCBs are potent inducers of ICAM-1 in endothelial cells. Researchers are performing tests at molecular, cellular and animal levels. These studies will help identify the fundamental signaling mechanisms underlying PCB-induced activation of ICAM-1 expression, tumor cell adherence, transmigration across the endothelium, and the progression of cancer metastasis.