During tumor growth, malignant cells invade normal adjacent tissues, and the tumor itself is invaded by endothelial cells that form the vascular network necessary to provide the neoplasm with adequate blood supply. Some tumor cells penetrate into the newly formed capillary network and into the systemic circulation, from where they egress at distant sites to form secondary tumors (metastases). A common feature of these processes is the extracellular matrix degradation required for tumor or endothelial cells breaching through histological barriers. In vascular endothelial cells the expression of extracellular matrix-degrading proteinases is finely modulated by a variety of growth factors capable to induce formation of blood capillaries (angiogenesis). Among these factors, basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) are the most potent angiogenesis inducers.

Our research interests focus on the mechanisms that regulate proteolytic activities involved in cell invasion, and on the regulation of endothelial cell expression of FGF-2 and VEGF during tumor development. We have found that tumor cells secrete a protein that induces FGF-2 expression in vascular endothelial cells. FGF-2 in turn stimulates the expression of VEGF through an autocrine mechanism. In addition, we have observed that several proteolytic activities involved in cell invasion are regulated by interaction with the cell membrane. Our ongoing research projects seek to 1) identify and characterize the tumor-derived factor that induces endothelial cell expression of FGF-2; 2) test the hypothesis that proteinase interactions with the cell membrane may generate intracellular signals and regulate cell functions with a mechanism(s) similar to those activated by growth factor interactions with cell membrane receptors.