Urokinase-dependent cell surface proteolysis and cancer

Abstract

Plasmin formation is an important and complex process in vivo. It involves two enzymes, two inhibitors, the substrate and specific receptors. Plasmin formation, dependent on the urokinase-type plasminogen activator (uPA), is discussed in its biochemical, regulatory and physiological aspects and its involvement in cancer malignancy analysed. The role of cell surface plasminogen activation in the processes of extracellular matrix degradation, basement membrane dissolution and cancer invasiveness and metastasis is now established in a variety of model systems. The ability of cells to produce plasmin on their surface, due to the presence of uPA and plasminogen receptors, is at the basis of the regulation of the plasminogen activating system in vivo. Synthesis, activity and localization of each component can be individually regulated thus providing the system with an enormous flexibility.