Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis.
Extracellular proteolysis is an absolute requirement for new blood vessel formation (angiogenesis). This review examines the role of the matrix metalloproteinase (MMP) and plasminogen activator (PA)-plasmin systems during angiogenesis. Specifically, a role for gelatinases (MMP-2, MMP-9), membrane-type 1 MMP (MMP-14), the urokinase-type PA receptor, and PA inhibitor 1 has been clearly defined in a number of model systems. The MMP and PA-plasmin systems have also been implicated in experimental vascular tumor formation, and their role during this process will be examined. Antiproteolysis, particularly in the context of angiogenesis, has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization.
Pepper
M S
MS
Department of Morphology, University Medical Center, Geneva, Switzerland. michael.pepper@medecine.unige.ch
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D005341:Fibrinolysin / Q000502:physiology*; D005342:Fibrinolysis; D020782:Matrix Metalloproteinases / Q000502:physiology*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology; D010960:Plasminogen Activators / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases