Premium
VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo
Author(s) -
ZHAI YIFAN,
NI JIAN,
JIANG GONGWei,
LU JIAMO,
XING LILY,
LINCOLN CLINT,
CARTER KENNETH C.,
JANAT FOUAD,
KOZAK DIANE,
XU SIMIN,
ROJAS LORENA,
AGGARWAL BHARAT B.,
RUBEN STEVE,
LI LUYUAN,
GENTZ REINER,
YU GUOLIANG
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.1.181
Subject(s) - vascular endothelial growth inhibitor , angiogenesis , angiogenesis inhibitor , cd30 , tumor necrosis factor alpha , biology , endothelial stem cell , cancer research , microbiology and biotechnology , cytokine , vascular endothelial growth factor a , vascular endothelial growth factor , immunology , in vitro , biochemistry , tumor cells , vegf receptors
A novel member of the tumor necrosis factor (TNF) family has been identified from the human umbilical vein endothelial cell cDNA library, named vascular endothelial growth inhibitor (VEGI). The VEGI gene was mapped to human chromosome 9q32. The cDNA for VEGI encodes a protein of 174 amino acid residues with the characteristics of a type II transmembrane protein. Its amino acid sequence is 20–30% identical to other members of the TNF family. Unlike other members of the TNF family, VEGI is expressed predominantly in endothelial 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 of vascularization in MC‐38 tumors that expressed soluble but not membrane‐bound VEGI or were transfected with control vector. The conditioned media from soluble VEGI‐expressing cells showed marked inhibitory effect on in vitro 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.—Zhai, Y., Ni, J., Jiang, G.‐W., Lu, J., Xing, L., Lincoln, C., Carter, K. C., Janat, F., Kozak, D., Xu, S., Rojas, L., Aggarwal, B. B., Ruben, S., Li, L.‐Y., Gentz, R., Yu, G.‐L. VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo . FASEB J. 13, 181‐189 (1999)