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Patient-derived organoids to study glycosylation dynamics during gastric disease
i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
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2025 (English)In: Cell Reports, ISSN 2639-1856, E-ISSN 2211-1247, Vol. 44, no 11, article id 116550Article in journal (Refereed) Published
Abstract [en]

Aberrant cellular glycosylation is a key event that accompanies and actively sustains gastric neoplastic transformation. Patient-derived organoids (PDOs) have recently emerged as promising ex vivo models to study human gastric diseases; however, their glycosylation landscape remains unknown. To evaluate gastric PDOs as avatars of in vivo tissue glycosylation, a biobank of gastric PDOs (n = 56) was generated from gastric mucosa samples of non-tumoral obese patients (n = 11), adjacent tumor mucosa (n = 26), and gastric tumor tissue (n = 19). PDOs reproduce distinct stages of gastric carcinogenesis and recapitulate the gastric tissue-associated glycosylation profiles. PDOs capture glycan inter- and intra-tumoral heterogeneity, which is maintained over time and upon biobanking and xenografting. Furthermore, expression of type I/II Lewis antigens is dynamically controlled by the PDO’s differentiation status, influencing Helicobacter pylori binding, mirroring the gastric epithelium-tissue interactions. This study establishes PDOs as robust ex vivo tools to study gastric glycan dynamics in both gastric physiological and pathological settings.

Place, publisher, year, edition, pages
Elsevier, 2025. Vol. 44, no 11, article id 116550
Keywords [en]
CP: cell biology, gastric cancer, gastric carcinogenesis, gastric mucosa, glycans, glycosylation, Helicobacter pylori, patient-derived organoids
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-247770DOI: 10.1016/j.celrep.2025.116550ISI: 001619316700001PubMedID: 41206866Scopus ID: 2-s2.0-105023545742OAI: oai:DiVA.org:umu-247770DiVA, id: diva2:2023482
Available from: 2025-12-19 Created: 2025-12-19 Last updated: 2025-12-19Bibliographically approved

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Borén, Thomas

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