Binding of gastrointestinal tumor cells to endothelial E- and P-selectin adhesion receptors leads to transient down-regulation of sLeX ligands in vitro

BACKGROUND AND AIMS. The prognostic relevance of sialyl Lewis X (sLeX) expression in colorectal and gastric cancer and its relevance to the hematogenous phase of tumor invasion is controversial. This study was designed to evaluate sLeX expression during tumor cell-endothelial cell interaction in vitro. METHODS. Adhesion and transendothelial penetration of MKN45, PaCa-2, WiDr, or Dan-G cells was analyzed by combined phase contrast-reflection interference contrast microscopy. In parallel, kinetics of membranous sLeX expression were examined fluorimetrically. To identify factor(s) which may be responsible for sLeX expression during tumor invasion tumor cells were treated with soluble immunomodulators, isolated endothelial plasma membranes, or E-selectin or P-selectin IgG fusion proteins. sLeX was then analyzed by flow cytometry. RESULTS. Fluorometric quantification of sLeX demonstrated an inverse correlation between basal sLeX expression level and adhesion capacity of the tumor cells. Unexpectedly, sLeX was strongly down-regulated on tumor cell membranes in the course of heterophilic cell-cell contacts. The process occurred transiently, with a maximum effect 30-60 min after introducing tumor cells to the endothelial monolayer. Binding of tumor cells to immobilized E- and P-selectin IgG globulin chimeras was shown to be responsible for this phenomenon. CONCLUSION. A transient loss of sLeX is necessary for gastrointestinal tumor cells to invade endothelial cells. Due to the transient nature of the decrease in sLeX the controversy about the prognostic relevance of sLeX expression in colorectal and gastric cancer may be rooted in the stage of tumor invasion at the time of sLeX measurement.