title: Gangliosides expressed on breast cancer cells are E-selectin ligands.
abstract: Cancer cell adhesion to vascular endothelium is a critical process in hematogenous metastasis. We hypothesized that breast cancer cells express ligands that bind under blood flow conditions to E-selectin expressed by endothelial cells. At a hemodynamic wall shear rate, BT-20 and MDA-MB-468 breast cancer cells adhered to cytokine-activated human umbilical cord vein endothelial cells (HUVECs) but not to anti-E-selectin monoclonal antibody treated HUVECs, demonstrating that adhesion was specifically mediated by E-selectin. Characterization of glycans expressed on breast cancer cells by a panel of antibodies revealed that BT-20 cells expressed sialyl Lewis X (sLe(x)) and sialyl Lewis A (sLe(a)) but MDA-MB-468 cells did not, suggesting that the former possess classical glycans involved in E-selectin mediated adhesion while the latter have novel binding epitopes. Protease treatment of the breast cancer cells failed to significantly alter the carbohydrate expression profiles, binding to soluble E-selectin-Ig chimera, or the ability of the cells to tether and roll on E-selectin expressed by HUVECs, indicating that glycosphingolipids are functional E-selectin ligands on these cells. Furthermore, extracted breast cancer cell gangliosides supported binding of E-selectin-Ig chimera and adhesion of E-selectin transfected cells under physiological flow conditions. In summary, our results demonstrate that breast cancer cells express sialylated glycosphingolipids (gangliosides) as E-selectin ligands that may be targeted for prevention of metastasis.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH 45701, United States.
authors.forename: Venktesh S
authors.initials: VS
authors.lastname: Shirure
authors.forename: Karissa A
authors.initials: KA
authors.lastname: Henson
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Schnaar
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Monica M
authors.initials: MM
authors.lastname: Burdick
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018395:CA-19-9 Antigen; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009844:Oligosaccharides / Q000378:metabolism; D010447:Peptide Hydrolases / Q000494:pharmacology; D000080506:Sialyl Lewis X Antigen
chemical_list: D018395:CA-19-9 Antigen; D019040:E-Selectin; D005732:Gangliosides; D008024:Ligands; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D010447:Peptide Hydrolases