VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo

A novel member of the tumor necrosis factor (TNF) family has been identifie d from the human umbilical vein endothelial cell cDNA library, named vascul ar endothelial growth inhibitor (VEGI). The VEGI gene was mapped to human c hromosome 9q32. The cDNA for VEGI encodes a protein of 174 amino acid resid ues with the characteristics of a type II transmembrane protein. Its amino acid sequence is 20-30% identical to other members of the TNF family. Unlik e other members of the TNF family, VEGI is expressed predominantly in endot helial cells. Local production of a secreted form of VEGI via gene transfer caused complete suppression of the growth of MC-38 murine colon cancers in syngeneic C57BL/6 mice. Histological examination showed marked reduction o f vascularization in MC-38 tumors that expressed soluble but not membrane-b ound VEGI or were transfected with control vector. The conditioned media fr om soluble VEGI-expressing cells showed marked inhibitory effect on in vitr o proliferation of adult bovine aortic endothelial cells. Our data suggest that VEGI is a novel angiogenesis inhibitor of the TNF family and functions in part by directly inhibiting endothelial cell proliferation. The results further suggest that VEGI maybe highly valuable toward angiogenesis-based cancer therapy.