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 adhesio n of peripheral blood cells to interleukin-1 (IL-1)-activated endothel ium. In the present study the authors evaluated the role of E-selectin -Sialyl Lewis x (SLe(x))/ Sialyl Lewis a (SLe(a)) interaction in media ting in vitro adhesion of two colon cancer cell lines, HT-29 and COLO 201, to human umbilical cord endothelial cells (HUVEC). Colon cancer c ell lines had a strong expression of blood group-related carbohydrate epitopes as evaluated by fluorescence-activated cell sorter (FAGS) ana lysis. 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 o f cells with two different antibodies directed against SLe(x) and anti bodies directed against related Lewis epitopes, Le(x) and Le(a), had n o significant effect on adhesion. Three antibodies directed against SL e(a) differed in their capacity to inhibit the adhesion of HT-29 and C OLO 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 o r number of glycoproteins, or to a difference in the amount of SLe(a) present on individual proteins, suggesting that presence and right pre sentation of SLe(a) epitope might be important for adhesion of colon c ancer cells. Finally, in the in vitro system used, adhesion of HT-29 a nd COLO 201 cells to activated HUVEC is mediated predominantly by E-se lectin/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.