Iwai K, Ishikura H, Kaji M, Sugiura H, Ishizu A, Takahashi C, Kato H, Tanabe T, Yoshiki T
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Int J Cancer. 1993 Jul 30;54(6):972-7. doi: 10.1002/ijc.2910540618.
Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.
研究了体外人胰腺癌与活化内皮细胞之间黏附相关的黏附分子。6种胰腺癌细胞系与未刺激的人脐静脉内皮细胞（HUVEC）之间存在基础黏附，只有当胰腺癌细胞表达唾液酸化路易斯a（SLea）和唾液酸化路易斯x（SLex）时，才会出现对活化HUVEC基础黏附的增强。用白细胞介素1-β（IL-1β）或肿瘤坏死因子-α（TNF-α）而非干扰素-γ（IFN-γ）激活HUVEC可产生基础黏附增强。在IL-1β和/或TNF-α诱导的基础黏附增强中观察到剂量依赖性和相加效应。黏附增加与HUVEC表面E-选择素（或ELAM-1）上调相关，且在25℃和4℃时均明显。抗E-选择素和抗SLea可阻断增强的黏附，而抗SLex（针对E-选择素另一种已知配体的抗体）则不能。这些证据共同表明，胰腺癌细胞与活化内皮细胞之间的黏附受IL-1β和TNF-α等细胞因子调节，并由胰腺癌细胞上的SLea和内皮细胞上的E-选择素介导。这些分子在胰腺癌细胞向炎症部位的血行转移中可能具有重要意义。
