Analysis of the glyco-code in pancreatic ductal adenocarcinoma identifies glycan-mediated immune regulatory circuits.
| Title: | Analysis of the glyco-code in pancreatic ductal adenocarcinoma identifies glycan-mediated immune regulatory circuits. |
|---|---|
| Authors: | Rodriguez E; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; Boelaars K; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; Brown K; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; Madunić K; Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.; van Ee T; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; Dijk F; Amsterdam UMC, Academic Medical Center Amsterdam, University of Amsterdam, Department of Pathology, Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.; Verheij J; Amsterdam UMC, Academic Medical Center Amsterdam, University of Amsterdam, Department of Pathology, Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.; Li RJE; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; Schetters STT; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; Meijer LL; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.; Le Large TYS; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.; Driehuis E; Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and UMC Utrecht, Utrecht, The Netherlands.; Clevers H; Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and UMC Utrecht, Utrecht, The Netherlands.; Bruijns SCM; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; O'Toole T; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; van Vliet SJ; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; Bijlsma MF; Amsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.; Wuhrer M; Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.; Kazemier G; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.; Giovannetti E; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.; Cancer Pharmacology Lab, AIRC Start-Up Unit, Fondazione Pisana per la Scienza, Pisa, Italy.; Garcia-Vallejo JJ; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands.; van Kooyk Y; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, Amsterdam, The Netherlands. y.vankooyk@amsterdamumc.nl. |
| Source: | Communications biology [Commun Biol] 2022 Jan 11; Vol. 5 (1), pp. 41. Date of Electronic Publication: 2022 Jan 11. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]- |
| MeSH Terms: | Carcinoma, Pancreatic Ductal*/genetics ; Carcinoma, Pancreatic Ductal*/immunology ; Carcinoma, Pancreatic Ductal*/metabolism ; Carcinoma, Pancreatic Ductal*/pathology ; Glycoproteins*/chemistry ; Glycoproteins*/genetics ; Glycoproteins*/immunology ; Glycoproteins*/metabolism ; Pancreatic Neoplasms*/genetics ; Pancreatic Neoplasms*/immunology ; Pancreatic Neoplasms*/metabolism ; Pancreatic Neoplasms*/pathology; Epithelial-Mesenchymal Transition/genetics ; Epithelial-Mesenchymal Transition/immunology ; Pancreas/metabolism ; Pancreas/pathology ; Polysaccharides/chemistry ; Polysaccharides/genetics ; Polysaccharides/immunology ; Polysaccharides/metabolism ; Glycosylation ; Humans |
| Abstract: | 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.; (© 2022. The Author(s).) |
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| Grant Information: | MSCA-ITN-2014-ETN No 642870 EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020); KWF VU2014-7200 KWF Kankerbestrijding (Dutch Cancer Society) |
| Substance Nomenclature: | 0 (Glycoproteins); 0 (Polysaccharides) |
| Entry Date(s): | Date Created: 20220112 Date Completed: 20220314 Latest Revision: 20221025 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8752754 |
| DOI: | 10.1038/s42003-021-02934-0 |
| PMID: | 35017635 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't