Gangliosides expressed on breast cancer cells are E-selectin ligands

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

Research output: Contribution to journalArticle

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

Fingerprint

E-Selectin
Gangliosides
Cells
Breast Neoplasms
Ligands
Endothelial cells
Umbilical Cord
Human Umbilical Vein Endothelial Cells
Glycosphingolipids
Adhesion
Polysaccharides
Cell Adhesion
Neoplasm Metastasis
Cell adhesion
Hemodynamics
Vascular Endothelium
Shear deformation
Epitopes
Blood
Peptide Hydrolases

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Gangliosides expressed on breast cancer cells are E-selectin ligands. / Shirure, Venktesh S.; Henson, Karissa A.; Schnaar, Ronald Lee; Nimrichter, Leonardo; Burdick, Monica M.

In: Biochemical and Biophysical Research Communications, Vol. 406, No. 3, 18.03.2011, p. 423-429.

Research output: Contribution to journalArticle

Shirure, Venktesh S. ; Henson, Karissa A. ; Schnaar, Ronald Lee ; Nimrichter, Leonardo ; Burdick, Monica M. / Gangliosides expressed on breast cancer cells are E-selectin ligands. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 406, No. 3. pp. 423-429.
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