Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis

Thromb Haemost. 2004 Mar;91(3):438-49. doi: 10.1160/TH03-12-0784.


In recent decades, evidence has been accumulating showing the important role of urokinase-type plasminogen activator (uPA) in growth, invasion, and metastasis of malignant tumours. The evidence comes from results with animal tumour models and from the observation that a high level of uPA in human tumours is associated with a poor patient prognosis. It therefore initially came as a surprise that a high tumour level of the uPA inhibitor plasminogen activator inhibitor-I (PAI-I) is also associated with a poor prognosis, the PAI-I level in fact being one of the most informative biochemical prognostic markers. We review here recent investigations into the possible tumour biological role of PAI-I, performed by animal tumour models, histological examination of human tumours, and new knowledge about the molecular interactions of PAI-I possibly underlying its tumour biological functions. The exact tumour biological functions of PAI-I remain uncertain but PAI-I seems to be multifunctional as PAI-I is expressed by multiple cell types and has multiple molecular interactions. The potential utilisation of PAI-I as a target for anti-cancer therapy depends on further mapping of these functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cell Membrane / metabolism
  • Disease Models, Animal
  • Endopeptidases / metabolism
  • Humans
  • Models, Biological
  • Models, Molecular
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Plasminogen Activator Inhibitor 1 / physiology*
  • Prognosis
  • Protein Binding
  • Protein Conformation
  • Vitronectin / metabolism


  • Antineoplastic Agents
  • Plasminogen Activator Inhibitor 1
  • Vitronectin
  • Endopeptidases