The role of plasminogen-plasmin system in cancer.

Components of the plasminogen-plasmin system participate in a wide variety of physiologic and pathologic processes, including tumor growth, invasion and metastasis, through their effect on angiogenesis and cell migration. These components are found in most tumors and their expression not only signifies their function but also carries a prognostic value. Their expression is in turn modulated by cytokines and growth factors, many of which are up-regulated in cancer. Though both tPA and uPA are expressed in tumor cells, uPA with its receptor (uPAR) is mostly involved in cellular functions, while tPA with its receptor Annexin II on endothelial surface, regulates intravascular fibrin deposition. Among the inhibitors of fibrinolysis, PAI-1 is a major player in the pathogenesis of many vascular diseases as well as in cancer. Therapeutic interventions, either using plasminogen activators or experimental inhibitor agents against PAI-1, have shown encouraging results in experimental tumors but not been verified clinically.