Importance of E‐selectin (ELAM‐1) and sialyl lewisa in the adhesion of pancreatic carcinoma cells to acttvated endothelium

Abstract

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 Lewis^a (SLe^a) and sialyl Lewis^x (SLe^x). Activation of HUVEC with interleukin l-β (IL-Iβ) or tumor necrosis factor-α (TNF-α), but not with interferon-γ (IFN-γ), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-I β and/or TNF-α. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-I) on HUVEC, and was evident at both 25°C and 4°C. Anti-E-selectin and anti-SLe^a blocked the augmented attachment, whereas anti-SLe^x, 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 β and TNF-α, and is mediated by SLe^a 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.