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

Oncogene volume 23, pages 6986–6990 (2004)Cite this article

Abstract

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.

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Acknowledgements

We thank Fabrice Olivier for his technical assistance. This work was supported by grants from the Communauté française de Belgique (Actions de Recherches Concertées), the Commission of European Communities (LSHC-CT-2003-503297), the Fonds National de la Recherche Scientifique (FNRS, Belgium), the Fédération Belge Contre le Cancer, the Fonds spéciaux de la Recherche (University of Liège), the Centre Anticancéreux près l'Université de Liège, the FB Assurances, the D.G.T.R.E. from the ‘Région Wallonne’, the Interuniversity Attraction Poles (I.U.A.P.) from the Federal Office for Scientific, Technical and Cultural Affairs (O.S.T.C., Brussels, Belgium).

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Authors and Affiliations

  1. Laboratory of Tumor and Development Biology, CRCE, University of Liège, Tour de Pathologie (B23), Sart Tilman, Liège, B-4000, Belgium

    Khalid Bajou, Catherine Maillard, Maud Jost, Jean-Michel Foidart & Agnès Noel

  2. Center for Molecular and Vascular Biology, Faculty of Medicine KU Leuven, Leuven, B-3000, Belgium

    Roger H Lijnen

  3. Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, KU Leuven, Leuven, B-3000, Belgium

    Ann Gils & Paul Declerck

  4. Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, B-3000, Belgium

    Peter Carmeliet

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  1. Khalid Bajou
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  2. Catherine Maillard
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Correspondence to Agnès Noel.

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Bajou, K., Maillard, C., Jost, M. et al. Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth. Oncogene 23, 6986–6990 (2004). https://doi.org/10.1038/sj.onc.1207859

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