Metalloproteases and urokinase in angiogenesis and tumor progression.

Following malignant transformation, tumor cells and their surrounding stroma produce a variety of growth factors and proteolytic enzymes to induce new capillary formation (angiogenesis) and matrix degradation to promote tumor development. Two key families of proteases, matrix metalloproteases (MMPs) and urokinase (uPA) are now strongly implicated in this process of angiogenesis and matrix degradation. Both MMPs and uPA are abundantly produced by various tumors where their level of expression can serve as prognostic markers. Using gene transfer techniques, overexpression of these proteases and their receptors enhances the invasive and metastatic potential of tumor cells. Furthermore, blockage of actions of MMPs and uPA by molecular and chemical approaches results in a marked decrease in tumor growth to further validate the significance of these enzymes as targets for anti-cancer therapy.