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

E-H Lin , C Salon , E Brambilla , Dimitri Lavillette (1) , J Szecsi , Cosset François-Loïc , J-L Coll

1 LEM - Laboratoire d'Ecologie Microbienne - UMR 5557

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.

Mots clés: Humans; Female; Animals; Mice; Viral Fusion Proteins; Cultured; Tumor Cells; Genetic; Cats; Genetic Vectors; Carcinoma; Promoter Regions; Transfection; Apoptosis; Plasmids; Bystander Effect; Endogenous Retroviruses; Feline; Giant Cells; Gibbon Ape; Leukemia Virus; Lung Neoplasms; Non-Small-Cell Lung; Oncolytic Virotherapy; Xenograft Model Antitumor Assays

Domaines: Sciences du Vivant [q-bio]

E-H Lin, C Salon, E Brambilla, Dimitri Lavillette, J Szecsi, et al.. Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer. Cancer Gene Therapy, 2010, 17 (4), pp.256-265. ⟨10.1038/cgt.2009.74⟩. ⟨hal-02548042⟩