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

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9432230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5500 (Electronic) Linking ISSN: 09291903 NLM ISO Abbreviation: Cancer Gene Ther Subsets: MEDLINE

Publication: <2002->: London : Nature Publishing Group
Original Publication: Norwalk, CT : Appleton & Lange, c1994-

Apoptosis* ; Oncolytic Virotherapy*; Carcinoma, Non-Small-Cell Lung/*therapy ; Giant Cells/*metabolism ; Lung Neoplasms/*therapy ; Viral Fusion Proteins/*metabolism; Animals ; Bystander Effect ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/virology ; Cats ; Endogenous Retroviruses/physiology ; Female ; Genetic Vectors/therapeutic use ; Giant Cells/virology ; Humans ; In Vitro Techniques ; Leukemia Virus, Feline/physiology ; Leukemia Virus, Gibbon Ape/physiology ; Lung Neoplasms/metabolism ; Lung Neoplasms/virology ; Mice ; Plasmids/genetics ; Promoter Regions, Genetic ; Transfection ; Tumor Cells, Cultured ; Viral Fusion Proteins/genetics ; Xenograft Model Antitumor Assays

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.

0 (Viral Fusion Proteins)

Date Created: 20091107 Date Completed: 20100608 Latest Revision: 20141120

20231215

10.1038/cgt.2009.74

19893593