Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer.
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.
Lin
E-H
EH
INSERM U823, Institut Albert Bonniot, Grenoble, France.
Salon
C
C
Brambilla
E
E
Lavillette
D
D
Szecsi
J
J
Cosset
F-L
FL
Coll
J-L
JL
D000818:Animals; D017209:Apoptosis; D024201:Bystander Effect; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D002415:Cats; D020077:Endogenous Retroviruses / Q000502:physiology; D005260:Female; D005822:Genetic Vectors / Q000627:therapeutic use; D015726:Giant Cells / Q000378:metabolism* / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D005256:Leukemia Virus, Feline / Q000502:physiology; D017989:Leukemia Virus, Gibbon Ape / Q000502:physiology; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D051379:Mice; D050130:Oncolytic Virotherapy; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D014760:Viral Fusion Proteins