Stimulation of Cancer Metastases in Systemic Inflammatory Response Syndrome

本实验研究了肿瘤坏死因子α(肿瘤坏死因子α)对胰腺癌细胞与人脐静脉内皮细胞的黏附反应及体内癌细胞肝转移的影响。经肿瘤坏死因子α刺激后，人脐静脉内皮细胞上中性粒细胞黏附分子E-选择素的表达增加。此外，胰腺癌细胞在肿瘤坏死因子α刺激后与中性粒细胞的粘附性增加。肿瘤坏死因子α诱导的黏附反应依赖于癌细胞表面唾液酸化Lewisα的表达程度。肿瘤坏死因子α浓度升高后，脾内接种高表达唾液酸路易斯α的癌细胞，常可观察到体内肝转移。由于癌细胞上的唾液酸化Lewis^a是E-选择素的配体，因此肿瘤坏死因子α上调了癌细胞上唾液酸化Lewis^a与人脐静脉内皮细胞上E-选择素之间的黏附。提示创伤后肿瘤坏死因子α的产生可能促进唾液酸化Lewisα高表达癌细胞的转移。

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.