Plasminogen activator inhibitor-1 in tumor growth, angiogenesis and vascular remodeling.
Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of urokinase type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), and as such is thought to play an important role in the regulation of extracellular matrix remodeling. In blood, PAI-1 is bound to the adhesion protein vitronectin and is associated with vitronectin in fibrin clots and the provisional matrix. Elevated levels of PAI-1 are associated with atherosclerosis and an increased thrombotic tendency, while PAI-1 deficiency leads to increased fibrinolysis and bleeding. PAI-1 is also elevated in many solid tumors and is associated with a poor prognosis in cancer. PAI-1 has been shown to be a potent regulator of both vascular cell migration in vitro and of angiogenesis and tumor growth in vivo. PAI-1 can both promote and inhibit tumor growth and angiogenesis. Low concentrations of PAI-1 can stimulate tumor angiogenesis while treatment of animals with high doses of PAI-1 inhibits angiogenesis and tumor growth. Hence, PAI-1 appears to have a multifunctional role in regulating the migratory and fibrinolytic activity of vascular cells, and this, in turn, may help to explain the many varied actions of PAI-1.
Stefansson
Steingrimur
S
Vascular Biology Department, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.
McMahon
Grainne A
GA
Petitclerc
Eric
E
Lawrence
Daniel A
DA
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use
D017395:Plasminogen Activator Inhibitor 1