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    N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny


    Kavanagh, Emma L. and Halasz, Melinda and Dowling, Paul and Withers, Jo and Lindsay, Sinéad and Higgins, Michaela J. and Irwin, Jane A. and Rudd, Pauline M. and Saldova, Radka and McCann, Amanda (2021) N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny. Molecular Omics, 17 (1). pp. 72-85. ISSN 2515-4184

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    Abstract

    Triple negative breast cancer (TNBC) has poor clinical outcomes and limited treatment options. Chemotherapy, while killing some cancer cells, can result in therapeutic-induced-senescent (TIS) cells. Senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Recently, N- and O-linked glycosylation alterations have been associated with senescence. We aimed to profile the N-linked glycans of whole cells, membrane, cytoplasm and EVs harvested from TIS TNBC cells and to compare these to results from non-senescent cells. TIS was induced in the Cal51 TNBC cells using the chemotherapeutic agent paclitaxel (PTX). Ultra-performance liquid chromatography (UPLC) analysis of exoglycosidase digested N-linked glycans was carried out on TIS compared to non-treated control cells. LC-Mass spectrometry (MS) analysis of the N-linked glycans and lectin blotting of samples was carried out to confirm the UPLC results. Significant differences were found in the N-glycan profile of the Cal51 membrane, cytoplasm and EV progeny of TIS compared to non-senescent cells. Protein mass spectrometry showed that the TIS cells contain different glycan modifying enzymes. The lectin, calnexin demonstrated a lower kDa size (B58 kDa) in TIS compared to control cells (B90 kDa) while Galectin 3 demonstrated potential proteolytic cleavage with 32 kDa and B22 kDa bands evident in TIS compared to non-senescent control cells with a major 32 kDa band only. TIS CAL51 cells also demonstrated a reduced adhesion to collagen I compared to control non-senescent cells. This study has shown that therapeutic-induced-senescent TNBC cells and their EV progeny, display differential N-glycan moieties compared to non-senescent Cal51 cells and their resultant EV progeny. For the future, N-glycan moieties on cancer senescent cells and their EV progeny hold potential for (i) the monitoring of treatment response as a liquid biopsy, and (ii) cancer senescent cell targeting with lectin therapies

    Item Type: Article
    Additional Information: Cite as: Kavanagh, E.L., Halasz, M., Dowling, P., Withers, J., Lindsay, S., Higgins, M.J., Irwin, J.A., Rudd, P.M., Saldova, R. and McCann, A. (2021) N -Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny. Molecular omics, 17 (1), 72-85.
    Keywords: Triple negative breast cancer; Chemotherapy; lectin therapies
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17263
    Identification Number: https://doi.org/10.1039/D0MO00017E
    Depositing User: Paul Dowling
    Date Deposited: 01 Jun 2023 11:07
    Journal or Publication Title: Molecular Omics
    Refereed: Yes
    URI:
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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