title: E-selectin: sialyl Lewis, a dependent adhesion of colon cancer cells, is inhibited differently by antibodies against E-selectin ligands.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Srinivas
authors.forename: P
authors.initials: P
authors.lastname: Påhlsson
authors.forename: A
authors.initials: A
authors.lastname: Lundblad
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D018395:CA-19-9 Antigen; D002118:Calcium / Q000494:pharmacology; D002241:Carbohydrates / Q000096:biosynthesis / Q000276:immunology; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D019040:E-Selectin / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D008024:Ligands; D000080506:Sialyl Lewis X Antigen; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002241:Carbohydrates; D019040:E-Selectin; D000939:Epitopes; D005732:Gangliosides; D007983:Lewis Blood Group Antigens; D008024:Ligands; D000080506:Sialyl Lewis X Antigen; C094688:sialyl Lewis(x) ganglioside; C064564:sialyl Le(a) ganglioside; D002118:Calcium