Secretion of extracellular superoxide dismutase from muscle transduced with recombinant adenovirus inhibits the growth of B16 melanomas in mice.
A number of reports have described the effects of oxidative stress on tumor growth. Therefore, these experiments were designed to test the hypothesis that overexpression of extracellular superoxide dismutase (ecSOD) would inhibit the growth of tumors arising from s.c. implantation of syngenic B16-F1 melanoma cells. C57BL/6 mice were infected i.m. with adenovirus containing either beta-galactosidase (Ad.lacZ) as control or the secreted extracellular isoform of SOD (Ad.ecSOD) 3 days before s.c. implantation of B16-F1 tumor cells. Serum SOD activity was elevated nearly approximately 5-fold over control animals. Two weeks after implantation, B16-F1 tumor size was 65% smaller in mice infected with Ad.ecSOD in comparison with mice infected with Ad.lacZ. However, the presence of SOD did not affect growth rates of B16-F1 cells in vitro. Consistent with smaller tumor volume, tumors from Ad.ecSOD-infected mice also expressed less vascular endothelial growth factor (VEGF). Moreover, in vitro studies using B16-F1 cells confirm that SOD blunts oxidant-dependent VEGF expression. Importantly, CD31 expression and vessel density were markedly reduced in tumors from Ad.ecSOD-infected mice compared with controls. These data suggest that tumor oxidative stress may facilitate tumor vascularization and thus promote tumor growth.
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. wheelmi@med.unc.edu
Michael D
MD
Wheeler
Olivia M
OM
Smutney
R Jude
RJ
Samulski
D000256:Adenoviridae; D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D005110:Extracellular Space / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000201:enzymology*; D018384:Oxidative Stress; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors; D014161:Transduction, Genetic; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism
D011994:Recombinant Proteins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001616:beta-Galactosidase