Natural and Synthetic Inhibitors of The Tumor-Associated Serine Protease Urokinase-Type Plasminogen Activator
2002
In the present overview, the multifunctional capacity of the uPA-system in tumor biological processes was emphasized. In addition to its central role in pericellular proteolysis, uPA/uPAR-mediated activities contribute to many different processes like cell proliferation, adhesion, migration, and angiogenesis. Whereas extracellular PAI-2 solely acts as an inhibitor of uPA (and tPA), PAI-1 clearly exerts additional functions, e. g. involvement in modulation of uPAR- and integrin-mediated cell adhesion as well as in redistribution of uPAR on the tumor cell surface supporting the reorganization of the invasive front. Selective synthetic active site inhibitors of uPA may serve as novel therapeutic agents for anti-invasive and anti-proliferative cancer therapy.
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