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Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model

Cancer Gene Therapy volume 15, pages 685–692 (2008)Cite this article

Abstract

Tissue-type plasminogen activator (tPA) plays a major role in the fibrinolytic system. According to several reports, tPA may also have antiangiogenic properties, especially in combination with a free sulfhydryl donor (FSD). In the rat C6 glioma model, in vitro and in vivo tPA synthesis by glioma cells is enhanced by differentiation therapy. To address the antiangiogenic potential of tPA in this model, tPA was overexpressed in glioma tumors by ex vivo transduction of C6 cells with a lentiviral vector encoding tPA. The transduced cells were subcutaneously implanted into nude mice. Gene transfer allowed for efficient synthesis of tPA by the C6 tumors. Although the treatment of tPA+ tumor-bearing animals with the FSD captopril generated angiostatin in situ and reduced endothelial vascularization of the tumors, it had no effect on tumor growth. Alternative mechanisms could account for this lack of effect and consequently have important implications for vascular the treatment of glioblastoma.

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Acknowledgements

We thank Annick Michoud, Annick Simon and Sylvie Heustache for technical assistance, and Dr Susan Gilson for her help with English writing. We are grateful to Inserm U318 (Pr AL Benabid, Pr F Berger) for in vivo experimentation and to the anatomy–pathology laboratory of Grenoble University Hospital (Pr E Brambilla, Pr B Pasquier) for preparation of tissue sections. This work was supported by a grant from the Groupement des Entreprises Françaises pour la lutte contre le cancer (GEFLUC).

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Authors and Affiliations

  1. DBPC, GREPI EA 2938, University Hospital of Grenoble, Grenoble, France

    F Solly, N Bolle, B Polack & G Pernod

  2. Division of Angiology and Hemostasis, Laboratory of Vascular Biology, Geneva University Hospital, Geneva, Switzerland

    R Fish & E Kruithof

  3. Laboratory of Neuroscience, INSERM U318, Grenoble, France

    B Simard

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  1. F Solly
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  7. G Pernod
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Correspondence to G Pernod.

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Solly, F., Fish, R., Simard, B. et al. Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model. Cancer Gene Ther 15, 685–692 (2008). https://doi.org/10.1038/cgt.2008.36

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