Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth.
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.
Laboratory of Tumor and Development Biology, CRCE, University of Liège, Tour de Pathologie (B23), Sart Tilman, B-4000 Liège, Belgium.
Khalid
K
Bajou
Catherine
C
Maillard
Maud
M
Jost
Roger H
RH
Lijnen
Ann
A
Gils
Paul
P
Declerck
Peter
P
Carmeliet
Jean-Michel
JM
Foidart
Agnès
A
Noel
D000818:Animals; D015603:Keratinocytes / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000209:etiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000502:physiology*
D017395:Plasminogen Activator Inhibitor 1