Stimulation of Cancer Metastases in Systemic Inflammatory Response Syndrome

本实验研究了肿瘤坏死因子α（TNF α）对胰腺癌细胞与人脐静脉内皮细胞（HUVECs）粘附反应及胰腺癌细胞肝转移的影响。TNF α刺激后，HUVECs上中性粒细胞粘附分子E-选择素表达增加。此外，胰腺癌细胞与HUVEC的粘附在TNF α刺激后增加，与中性粒细胞一样。TNF α诱导的粘附反应依赖于癌细胞上sialyl刘易斯^a表达的程度。当表达大量唾液酸刘易斯^a的癌细胞在血浆TNF α浓度升高后脾内接种时，经常观察到体内肝转移。由于癌细胞上的sialyl刘易斯^a是E-选择素的配体，如同中性粒细胞上的sialyl刘易斯^x，TNF α上调癌细胞上的sialyl刘易斯^a与HUVEC上的E-选择素之间的粘附。这些结果表明，手术创伤后TNF α的产生可能刺激具有高sialyl刘易斯^a表达的癌细胞的转移。

We studied the effect of tumor necrosis factor α (TNF α), one of the major inflammatory cytokines, on the adhesive reaction of pancreatic cancer cells to human umbilical vein endothelial cells (HUVECs) and on the hepatic metastasis of cancer cells in vivo. After TNF α stimulation, the expression of E-selectin, an adhesion molecule to neutrophils on HUVECs, increased. In addition, the adhesion of pancreatic cancer cells to HUVECs increased after TNF α stimulation, as was observed with neutrophils. The TNF α-induced adhesive response depended on the extent of sialyl Lewis^a expression on cancer cells. The hepatic metastasis in vivo was often observed when cancer cells expressing a high amount of sialyl Lewis^a were inoculated intrasplenically after increase in plasma TNF α concentration. Because sialyl Lewis^a on cancer cells is a ligand for E-selectin, as sialyl Lewis^x on neutrophils, TNF α upregulated the adhesion between sialyl Lewis^a on cancer cells and E-selectin on HUVECs. These results suggest that production of TNF α after surgical trauma may stimulate the metastasis of cancer cells with high sialyl Lewis^a expression.