E-Selectin: Sialyl Lewis, a Dependent Adhesion of Colon Cancer Cells, is Inhibited Differently by Antibodies Against E-Selectin Ligands

Recent studies have demonstrated that selectins, a new family of cell-adhesion molecules with similar domain structures, mediate the adhesion of peripheral blood cells to interleukin-1 (IL-1)-activated endothelium. In the present study the authors evaluated the role of E-selectin-Sialyl Lewis x (SLe^x)/Sialyl Lewis a (SLe^a) interaction in mediating in vitro adhesion of two colon cancer cell lines, HT-29 and COLO 201, to human umbilical cord endothelial cells (HUVEC). Colon cancer cell lines had a strong expression of blood group-related carbohydrate epitopes as evaluated by fluorescence-activated cell sorter (FACS) analysis. It was established that adhesion of HT-29 and COLO 201 cells to IL-1 stimulated HUVEC was calcium dependent and could be inhibited by a monoclonal antibody directed against E-selectin. Prior incubation of cells with two different antibodies directed against SLe^x and antibodies directed against related Lewis epitopes, Le^x and Le^a, had no significant effect on adhesion. Three antibodies directed against SLe^a differed in their capacity to inhibit the adhesion of HT-29 and COLO 201 cells to HUVEC. Only one antibody directed against the SLe^a structure was effective in inhibiting adhesion of both COLO 201 and HT-29 cells. The difference could not be attributed to titre, the type or number of glycoproteins, or to a difference in the amount of SLe^a present on individual proteins, suggesting that presence and right presentation of SLe^a epitope might be important for adhesion of colon cancer cells. Finally, in the in vitro system used, adhesion of HT-29 and COLO 201 cells to activated HUVEC is mediated predominantly by E-selectin/SLe^a interaction. SLe^x and related epitopes, Le^x and Le^a, seem to have limited relevance for colon cancer cell recognition of E-selectin.