Journal Articles
Journal Articles Recent Res. Devel. Cancer, 2 (2000): 1-12
The Urokinase Plasminogen Activator Receptor (uPAR) is a Chokepoint for Carcinoma Metastasis and Angiogenesis
Andrew P. Mazar, Susan Gawlak, Ronald H. Goldfarb, Richard P. Kitson, Shafaat A. Rabbani, Yongjing Guo, Allen M. Gown and Terence R. Jones
Abstract
The urokinase plasminogen activator system has been demonstrated to be central to events associated with the motility of various cell types including leukocytes, tumor cells and angiogenic endothelial cells. This system consists of several components including the serine protease urokinase plasminogen activator (uPA), its cell-surface receptor (uPAR), plasminogen and inhibitors of the system including plasminogen activator inhibitors (PAIs) and α2-antiplasmin. The activities of this system are initiated and mediated at the cell surface via uPAR, which is central to both the extracellular proteolytic activities as well as the intracellular signaling pathways that are responsible for the matrix remodeling , cell morphology changes and diapedesis and growth factor activation that lead to cell motility. In this review, we present our hypothesis that based on its central role in the above-mentioned processes, the uPA system and especially uPAR represents a chokepoint for the modulation of cell motility associated with tumor metastasis and angiogenesis. Finally, we present data on the therapeutic and diagnostic utility of targeting this system, especially for the detection and inhibition of tumor angiogenesis.