Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth

Oncogene. 2004 Sep 9;23(41):6986-90. doi: 10.1038/sj.onc.1207859.


Plasminogen activator inhibitor type 1 (PAI-1) plays a key role in tumor progression and is believed to control proteolytic activity and cell migration during angiogenesis. We report here that host PAI-1, at physiological concentration, promotes in vivo tumor invasion and angiogenesis. In sharp contrast, inhibition of tumor vascularization was observed when PAI-1 was produced at supraphysiologic levels, either by host cells (transgenic mice overexpressing PAI-1) or by tumor cells (after transfection with murine PAI-1 cDNA). This study provides for the first time in vivo evidence for a dose-dependent effect of PAI-1 on tumor angiogenesis. Of great interest is the finding that PAI-1 produced by tumor cells, even at high concentration, did not overcome the absence of PAI-1 in the host, emphasizing the importance of the cellular source of PAI-1.

MeSH terms

  • Animals
  • Keratinocytes / pathology
  • Mice
  • Neoplasm Invasiveness
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / pathology
  • Neovascularization, Pathologic / etiology*
  • Plasminogen Activator Inhibitor 1 / analysis
  • Plasminogen Activator Inhibitor 1 / physiology*


  • Plasminogen Activator Inhibitor 1