Our laboratory is primarily interested in studying how integrin-mediated cellular communication with the extracellular matrix (ECM) regulates angiogenesis, tumor growth and metastasis. In particular, we study the cellular and molecular mechanisms by which the cooperative interactions between integrin receptors and proteolytic enzymes regulate the exposure of cryptic ECM epitopes that modulate endothelial and tumor cell behavior. We are currently characterizing these unique cryptic ECM regulatory elements in an attempt to understanding how integrin receptor binding to these control sites regulate signaling pathways that contribute to angiogenesis and tumor progression. Surprisingly, inhibition of cellular interactions with one of these cryptic ECM control elements significantly increased expression of insulin-like growth factor binding protein-4 (IGFBP-4) as well as the well-known endogenous angiogenesis inhibitor TSP-1. In this regard, we have recently demonstrated the possibility that targeting these non-cellular cryptic epitopes may represent a unique clinical strategy for controlling malignant cell behavior. In summary, we utilize a combination of in vitro cellular, molecular and biochemical assays in conjunction with several in vivo models in attempts to develop novel strategies for the treatment of pathological angiogenesis and malignant tumor growth progression.