A functional glycoproteomics approach identifies CD13 as a novel E-selectin ligand in breast cancer

Biochimica Et Biophysica Acta. General Subjects
Mylène A CarrascalPaula A Videira

Abstract

The glycan moieties sialyl-Lewis-X and/or -A (sLeX/A) are the primary ligands for E-selectin, regulating subsequent tumor cell extravasation into distant organs. However, the nature of the glycoprotein scaffolds displaying these glycans in breast cancer remains unclear and constitutes the focus of the present investigation. We isolated glycoproteins that bind E-selectin from the CF1_T breast cancer cell line, derived from a patient with ductal carcinoma. Proteins were identified using bottom-up proteomics approach by nanoLC-orbitrap LTQ-MS/MS. Data were curated using bioinformatics tools to highlight clinically relevant glycoproteins, which were validated by flow cytometry, Western blot, immunohistochemistry and in-situ proximity ligation assays in clinical samples. We observed that the CF1_T cell line expressed sLeX, but not sLeA and the E-selectin reactivity was mainly on N-glycans. MS and bioinformatics analysis of the targeted glycoproteins, when narrowed down to the most clinically relevant species in breast cancer, identified CD44 glycoprotein (HCELL) and CD13 as key E-selectin ligands. Additionally, the co-expression of sLeX-CD44 and sLeX-CD13 was confirmed in clinical breast cancer tissue samples. Both CD44 and CD13 gly...Continue Reading

Citations

Jun 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Charles J Dimitroff
Jan 9, 2020·Biochimica Et Biophysica Acta. General Subjects·Martina PirroPaul J Hensbergen
Nov 11, 2020·International Journal of Molecular Sciences·Fanny M DeschepperPaula A Videira
Mar 24, 2021·Analytical and Bioanalytical Chemistry·Hui LuDan Liu
Jun 3, 2021·Cancers·Elisenda Alsina-SanchisAndreas Fischer

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