Urokinase Plasminogen Activator System: A Multifunction Role in Tumor Progression and Metastasis

Abstract

The urokinase plasminogen activator (uPA) system is central to a spectrum of biologic processes including fibrinoloysis, inflammation, atherosclerotic plaque formation, matrix remodeling during wound healing, tumor invasion, angiogenesis, and metastasis. Binding of uPA with its receptor (uPAR) initiates a proteolytic cascade that results in the conversion of plasminogen to plasmin. Plasmin through its own proteolytic function degrades a range of extracellular basement membrane components and activates others such as the metalloproteinases. Independent of catalytic activity, uPAR also is involved in cell signaling, interactions with integrins, cell motility, adhesion and invasion, and angioge..