PAI-1; cancer invasion; tumoral angiogenesis; serine protease; protease inhibitor
Abstract :
[en] 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.
Bajou, Khalid ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire
Maillard, Catherine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Jost, M.
Lijnen, R. H.
Gils, A.
Declerck, P.
Carmeliet, P.
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Language :
English
Title :
Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth
Publication date :
09 September 2004
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, Basingstoke, United Kingdom
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