In vitro remodeling of tumor vascular endothelial cells using conditioned medium from various tumor cells and their sensitivity to TNF-alpha

Prevention of tumor-associated blood vessel formation (angiogenesis) is pot entially powerful strategy to treat cancer. We found that tumor vascular en dothelial cells were rearranged in vitro with conditioned culture medium de rived from tumor cells and compared the sensitivity to the effects of TNF-a lpha between normal and tumor endothelial cells, incubation with tumor (Met h-A, Colon26)-derived conditioned medium showed that no effect was observed on cell growth. Tumor cells (Meth-A, Colon26, and B16BL6) only showed no s ensitivity to TNF-alpha. Normal and control endothelial cells in culture sh owed little cytotoxicity in response to TNF-alpha treatment, but marked cyt otoxicity of TNF-alpha was observed in endothelial cells cultured with tumo r-derived conditioned medium. Sensitivity to TNF-alpha was different depend ing on the type of tumor from. which the conditioned medium was derived. Th is difference in sensitivity was assumed to be due to the in vivo sensitivi ty to TNF-alpha. The results of this study suggested that the sensitivity o f tumors to TNF-alpha is controlled by the sensitivity of tumor vasculature . (C) 2000 Academic Press.