ArticlePloS one2013
Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Tumor glycosylation engages CD301b-mediated myeloid regulation in breast cancer.Research square · 2026Article
- CD301b lectin expression in the breast tumor microenvironment augments tumor growth.Research square · 2025Article
- CD301b lectin expression in the breast tumor microenvironment augments tumor growth.bioRxiv : the preprint server for biology · 2025Article
- The Role of Mucins in Cancer and Cancer Progression: A Comprehensive Review.Current issues in molecular biology · 2025Review
- The multifaceted roles of mucins family in lung cancer: from prognostic biomarkers to promising targets.Frontiers in immunology · 2025Review
- Collagen Mineralization Decreases NK Cell-Mediated Cytotoxicity of Breast Cancer Cells via Increased Glycocalyx Thickness.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Development of a prognostic model for NSCLC based on differential genes in tumour stem cells.Scientific reports · 2024Article
- Immunoengineering can overcome the glycocalyx armour of cancer cells.Nature materials · 2024Article
- COLLAGEN MINERALIZATION DECREASES NK CELL-MEDIATED CYTOTOXICITY OF BREAST CANCER CELLS VIA INCREASED GLYCOCALYX THICKNESS.bioRxiv : the preprint server for biology · 2024Article
- MUC1 and MUC16: critical for immune modulation in cancer therapeutics.Frontiers in immunology · 2024Review
- CRISPR-screen identifies ZIP9 and dysregulated Zn2+ homeostasis as a cause of cancer-associated changes in glycosylation.Glycobiology · 2023Article
- Mucin Glycans: A Target for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Targeting Solid Cancers with a Cancer-Specific Monoclonal Antibody to Surface Expressed Aberrantly O-glycosylated Proteins.Molecular cancer therapeutics · 2023Article
- Emerging Roles of the Unique Molecular Chaperone Cosmc in the Regulation of Health and Disease.Biomolecules · 2022Review
- Altered glycosylation in pancreatic cancer and beyond.The Journal of experimental medicine · 2022Review
- Focusing on NK cells and ADCC: A promising immunotherapy approach in targeted therapy for HER2-positive breast cancer.Frontiers in immunology · 2022Review
- Mapping of truncated O-glycans in cancers of epithelial and non-epithelial origin.British journal of cancer · 2021Article
- Mucin-Type O-GalNAc Glycosylation in Health and Disease.Advances in experimental medicine and biology · 2021Article
- Tn Antigen Expression Contributes to an Immune Suppressive Microenvironment and Drives Tumor Growth in Colorectal Cancer.Frontiers in oncology · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr), STn (NeuAcα2-6GalNAc-Ser/Thr), T (Galβ1-3GalNAc-Ser/Thr), and ST (NeuAcα2-6Galβ1-3GalNAc-Ser/Thr) antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn). Glyco-engineering was performed by zinc finger nuclease (ZFN) knockout (KO) of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC) and cytotoxic T lymphocyte (CTL)-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells.
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