Gangliosides expressed on breast cancer cells are E-selectin ligands

Venktesh S. Shirure, Karissa A. Henson, Ronald L. Schnaar, Leonardo Nimrichter, Monica M. Burdick

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)423-429
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume406
Issue number3
DOIs
StatePublished - Mar 18 2011

Keywords

  • Cell adhesion
  • Metastasis
  • Shear rate
  • Sialyl Lewis
  • Sialyl Lewis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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