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Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer

Cancer Gene Therapy volume 17, pages 256–265 (2010)Cite this article

Abstract

Fusogenic membrane glycoproteins (FMGs) are viral envelope proteins, which bind surface receptors and induce fusion of the cell membrane. An FMG-transfected cell will fuse with neighbor cells, thus forming syncytia that die within 5 days. In this report, plasmids encoding for FMGs from Human Endogenous Retrovirus-W (HERV-W) was compared with Gibbon Ape Leukemia Virus (GALV) and feline endogenous virus RD-114 (RD). These plasmids were transfected in human non-small-cell lung cancer (NSCLC) cells in vitro or directly injected into tumors in mice. All FMGs induced the formation of syncytia containing around 50 cells. HERV-W or GALV FMGs decreased up to 80% of cell viability in vitro and inhibited tumor growth in vivo (60–70% reduction). In contrast, RD FMG was not efficient. Apoptosis played a role in the death of the syncytia, but addition of the caspase inhibitor Z-VAD-fmk had no effect, suggesting that apoptosis is not the only mechanism responsible for FMG-induced cell death. Altogether, our results demonstrate that even at very low transfection efficiency, the antitumor activity of HERV-W FMG is as effective as that of GALV in vitro and in vivo for the treatment of human lung tumors.

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Acknowledgements

This work was supported by the Institut National de la Santé Et de la Recherche Médicale (INSERM), The University Joseph Fourier, the Institut National du Cancer (INCA), the Cancéropôle Lyon-Rhône-Alpes-Auvergne (CLARA), the Association for Research on Cancer (ARC, France), the Agence Nationale pour la Recherche (ANR) and the Region Rhône-Alpes.

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Authors and Affiliations

  1. INSERM U823, Institut Albert Bonniot, Grenoble, France

    E-H Lin, C Salon, E Brambilla & J-L Coll

  2. Université Joseph Fourier, Grenoble, France

    E-H Lin, C Salon, E Brambilla & J-L Coll

  3. Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan

    E-H Lin

  4. INSERM U758, Lyon, France

    D Lavillette, J Szecsi & F-L Cosset

  5. Ecole Normale Supérieure de Lyon, Lyon, France

    D Lavillette, J Szecsi & F-L Cosset

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  1. E-H Lin
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Correspondence to J-L Coll.

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Lin, EH., Salon, C., Brambilla, E. et al. Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer. Cancer Gene Ther 17, 256–265 (2010). https://doi.org/10.1038/cgt.2009.74

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