Regulation of cancer invasion and vascularization by plasminogen activatorinhibitor-1

Acquisition of invasive/metastaticpotential through protease expression is a key event in tumor progression. The proteolytic enzyme plasmin is generat ed from the precursor plasminogen by the action of urokinase-type plasminog en activator (urokinase, uPA) or tissue-type plasminogen activator (tPA). P lasminogen activator inhibitor-1 or PAI-1 is the main inhibitor of uPA and tPA. High levels of components of this proteolytic system, including UPA an d its cell surface receptor (uPAR), have been correlated with a poor progno sis for different cancers. It was therefore anticipated that PAI-1 expressi on would be associated with favorable outcome. Paradoxically, high rather t han low PAI-1 levels predict poor survival of patients suffering from a var iety of cancers. Recent observations indicate a much more complex role of P AI-1 in tumor progression and angiogenesis than initially expected. The exa ct mechanisms of this multifunctional molecule remain puzzling. (C) 1999 Ha rcourt Publishers Ltd.