Tumor necrosis factor alpha acts on cultured human vascular endothelial cells to increase the adhesion of pancreatic cancer cells

We studied the effect of tumor necrosis factor alpha (TNF alpha), one of th e major inflammatory cytokines, on the adhesive reaction of pancreatic canc er cells to human umbilical vein endothelial cells (HUVECs) and on the hepa tic metastasis of cancer cells in vivo. After TNF alpha stimulation, the ex pression of E-selectin, an adhesion molecule to neutrophils on HUVBCs, incr eased. In addition, the adhesion of pancreatic cancer cells to HUVECs incre ased after TNF alpha stimulation, as was observed with neutrophils. The TNF alpha -induced adhesive response depended on the extent of sialyl Lewis(a) expression on cancer cells. The hepatic metastasis in vivo was often obser ved when cancer cells expressing a high amount of sialyl Lewis(a) were inoc ulated intrasplenically after increase in plasma TNF alpha concentration by lipopolysaccharide administration. Because sialyl Lewis(a) on cancer cells is a ligand for E-selectin on HUVECs, as sialyl Lewis(x) on neutrophils, T NF alpha upregulated the adhesive interaction between sialyl Lewis(a) on ca ncer cells and E-selectin on HUVECs. These results suggest that production of TNF alpha after surgical trauma may stimulate the hematogenic metastasis of cancer cells with a high sialyl Lewis(a) expression.