The plasminogen activator system and cancer.
The fibrinolytic system, more appropriately referred to as the plasminogen activator system, controls not only the intravascular fibrin deposition but also participates in a wide variety of physiologic and pathologic processes. In cancer, the components of this system are involved in tumor growth, invasion and metastasis, through their effect on angiogenesis and cell migration. These components are found in most tumors and their expression signifies not only 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 plasminogen activators, 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 intervention, either using plasminogen activators or use of experimental inhibitor agents against PAI-1, has shown encouraging results in experimental tumors but not verified clinically. Information provided in this brief review is aimed to promote greater interest in the role of the plasminogen activator system in cancer.
McMahon
Brandon
B
Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Kwaan
Hau C
HC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D025901:Carboxypeptidase B2 / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology; D018000:Receptors, Peptide / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator / Q000502:physiology; D019851:Thrombophilia / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D013927:Thrombosis / Q000097:blood / Q000209:etiology*; D010959:Tissue Plasminogen Activator / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D018000:Receptors, Peptide; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; C514873:annexin II receptor, human; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator