Analysis of the glyco-code in pancreatic ductal adenocarcinoma identifies glycan-mediated immune regulatory circuits.

Carcinoma, Pancreatic Ductal / genetics Epithelial-Mesenchymal Transition / genetics Glycoproteins / chemistry Glycosylation Humans Pancreas / metabolism Pancreatic Neoplasms / genetics Polysaccharides / chemistry

Journal

Communications biology

ISSN: 2399-3642

Titre abrégé: Commun Biol

Pays: England

ID NLM: 101719179

Informations de publication

Date de publication:
11 01 2022

Historique:

received: 01 07 2021

accepted: 30 11 2021

entrez: 12 1 2022

pubmed: 13 1 2022

medline: 15 3 2022

Statut: epublish

Résumé

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a 5-year survival rate of only 9%. Despite the fact that changes in glycosylation patterns during tumour progression have been reported, no systematic approach has been conducted to evaluate its potential for patient stratification. By analysing publicly available transcriptomic data of patient samples and cell lines, we identified here two specific glycan profiles in PDAC that correlated with progression, clinical outcome and epithelial to mesenchymal transition (EMT) status. These different glycan profiles, confirmed by glycomics, can be distinguished by the expression of O-glycan fucosylated structures, present only in epithelial cells and regulated by the expression of GALNT3. Moreover, these fucosylated glycans can serve as ligands for DC-SIGN positive tumour-associated macrophages, modulating their activation and inducing the production of IL-10. Our results show mechanisms by which the glyco-code contributes to the tolerogenic microenvironment in PDAC.

Identifiants

DOI: 10.1038/s42003-021-02934-0 PMID: 35017635 PMC: PMC8752754

pubmed: 35017635

doi: 10.1038/s42003-021-02934-0

pii: 10.1038/s42003-021-02934-0

pmc: PMC8752754

doi:

Substances chimiques

Glycoproteins 0

Polysaccharides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

Subventions

Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)

ID : MSCA-ITN-2014-ETN No 642870

Organisme : KWF Kankerbestrijding (Dutch Cancer Society)

ID : KWF VU2014-7200

Informations de copyright

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