Die Bindung gastrointestinaler Tumorzellen an endotheliales E- oder P-Selektin induziert eine transiente Reduktion der sLeX Liganden in vitro

Abstract

Sialyl Lewis X (sLeX) expression was analyzed in several gastrointestinal tumor cell lines and related to the ability of the tumor cells to adhere to endothelial cells in vitro. sLeX expression kinetics during the phase of tumor cell-endothelial cell interaction was also evaluated using a dynamic coculture invasion assay. The tumor cells differentially adhered to endothelial cells. However, although anti-sLeX monoclonal antibodies significantly reduced adhesion of the tumor cells to endothelium and prevented tumor cell binding to immobilized E-selectin, quantification of sLeX demonstrated an inverse correlation between sLeX expression level and adhesion capacity of the tumor cells. Most surprisingly, sLeX was downregulated in the course of heterophilic cell-cell contacts. The process occured transiently, with a maximum effect 30–60 min after the experimental onset. Binding of tumor cells to immobilized E- and P-selectin IgG globulin chimeras was shown to be responsible for this phenomenon. We conclude from our studies that the transient loss of sLeX is necessary to allow gastrointestinal tumor cells to procede in the transendothelial invasion cascade.