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Expression of the thrombospondin 1 fragment 167–569 in C6 glioma cells stimulates tumorigenicity despite reduced neovascularization

Oncogene volume 23, pages 3642–3649 (2004)Cite this article

Abstract

Gliomas are among the most malignant and most highly vascularized human tumors. We studied the therapeutic action of an angiostatic fragment of human thrombospondin 1 (named TSP1ang) on experimental glioma tumor growth. TSP1ang (enclosing amino acids 167–569) comprised the procollagen-homology domain and the three type I repeats of the original molecule. C6 glioma cells that stably express TSP1ang were generated, and their rate of in vitro growth did not appear to differ from that of C6 cells transfected with an empty plasmid. TSP1ang-expressing C6 cells were then injected either subcutaneously or intracerebrally into nude mice. The resulting tumors appeared to be less vascularized, but unexpectedly started to grow earlier and had a much more invasive phenotype than tumors derived from control C6 cells. They were also much more aggressive, since the mice bearing intracerebral TSP1ang-expressing tumor cells died before day 19 post-implantation, whereas all mice bearing control C6 tumors were alive at this time point. These results indicate that careful attention should be paid at designing smaller fragments from the multimodular angiostatic molecule TSP1 since, as observed in this study, it may unmask protumorigenic properties that counteract its antiangiogenic activity.

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Acknowledgements

We thank Mrs Monique Delon and Maryse Samuel for their expert technical assistance. This work was supported by the Institut National de la Santé et de la Recherche Médicale (EMI 01-05), the Commissariat à l'Energie Atomique (DSV/DRDC/ANGIO), the Ligue Nationale contre le Cancer (Comités de la Drôme et de l'Isère) and the Groupement des Entreprises Françaises pour la Lutte contre le Cancer (GEFLUC).

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Authors and Affiliations

  1. Department of Cellular Response and Dynamics, INSERM EMI 01-05, CEA-G, DRDC/ANGIO, 17 Rue des Martyrs, Grenoble, Cedex 09, F-38054, France

    Florence de Fraipont, Michelle Keramidas, Edmond M Chambaz & Jean-Jacques Feige

  2. Department of Integrative Biology, University Hospital of Grenoble, Grenoble, F-38043, France

    Florence de Fraipont & Michelle El Atifi

  3. INSERM U318, University Hospital of Grenoble, Grenoble, F-38043, France

    François Berger

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  1. Florence de Fraipont
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Correspondence to Jean-Jacques Feige.

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de Fraipont, F., Keramidas, M., El Atifi, M. et al. Expression of the thrombospondin 1 fragment 167–569 in C6 glioma cells stimulates tumorigenicity despite reduced neovascularization. Oncogene 23, 3642–3649 (2004). https://doi.org/10.1038/sj.onc.1207438

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