Inhibition of angiogenesis and breast cancer xenograft tumor growth by VEGI, a novel cytokine of the TNF superfamily

Recently, we reported a novel protein of the tumor necrosis factor (TNF) su perfamily, named vascular endothelial cell growth inhibitor (VEGI), which i s expressed predominantly in endothelial cells. When a secreted form of thi s new protein was overexpressed in mouse colon cancer cells, the growth of tumors formed by these cells in black mice was inhibited. We now report tha t recombinant VEGI inhibits the proliferation of endothelial cells but not that of other types of cells examined. The protein also inhibits formation of capillary-like structures by endothelial cells in collagen gels, and the growth of capillaries into collagen gels placed on the chick chorioallanto ic membrane. The anticancer potential of VEGI was examined in a breast canc er xenograft tumor model in which the cancer cells were co-injected with Ch inese hamster ovary cells overexpressing a secreted form of the protein. Th e co-injection resulted in potent. inhibition of xenograft tumor growth. Ou r findings are consistent with the view that VEGI is an endothelial cell-sp ecific negative regulator of angiogenesis, (C) 1999 Wiley-Liss, Inc.