Plasminogen activator inhibitor-1 in tumor growth, angiogenesis and vascular remodeling

Steingrimur Stefansson, Grainne A. McMahon, Eric Petitclerc, Daniel A. Lawrence*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

156 Citations (Scopus)


Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of urokinase type plasminogen activator (uPA) an 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.

Original languageEnglish
Pages (from-to)1545-1564
Number of pages20
JournalCurrent Pharmaceutical Design
Issue number19
Publication statusPublished - 2003

Other keywords

  • Angiogenesis
  • Extracellular matrix remodeling
  • Fibrinolysis
  • Migration
  • PAI-1
  • Plasminogen
  • Plasminogen activator inhibitor-1
  • Restenosis
  • Serpin
  • Tumor
  • uPA
  • Vitronectin


Dive into the research topics of 'Plasminogen activator inhibitor-1 in tumor growth, angiogenesis and vascular remodeling'. Together they form a unique fingerprint.

Cite this