Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis

Extracellular proteolysis is an absolute requirement for new blood vessel f ormation (angiogenesis). This review examines the role of the matrix metall oproteinase (MMP) and plasminogen activator (PA)-plasmin systems during ang iogenesis. Specifically, a role for gelatinases (MMP-2, MMP-9), membrane-ty pe 1 MMP (MMP-14), the urokinase-type PA receptor, and PA inhibitor I has b een clearly defined in a number of model systems. The MMP and PA-plasmin sy stems have also been implicated in experimental vascular tumor formation, a nd their role during this process will be examined. Antiproteolysis, partic ularly in the context of angiogenesis, has become a key target in therapeut ic strategies aimed at inhibiting tumor growth and other diseases associate d with neovascularization.