Gangliosides expressed on breast cancer cells are E-selectin ligands |
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Authors: | Shirure Venktesh S Henson Karissa A Schnaar Ronald L Nimrichter Leonardo Burdick Monica M |
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Institution: | aDepartment of Chemical and Biomolecular Engineering, Ohio University, Athens, OH 45701, United States;bBiomedical Engineering Program, Ohio University, Athens, OH 45701, United States;cDepartment of Pharmacology and Molecular Sciences and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States;dInstituto de Microbiologia Professor Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil |
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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 (sLex) and sialyl Lewis A (sLea) 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. |
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Keywords: | Abbreviations: CHO-E E-selectin transfected Chinese hamster ovary cells E&ndash Ig chimera recombinant mouse E-Selectin/human immunoglobulin Fc chimera FBS fetal bovine serum FITC fluorescein isothiocyanate HUVECs human umbilical cord vein endothelial cells mAbs monoclonal antibodies PE phycoerythrin sLea sialyl Lewis A sLex sialyl Lewis X |
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