Patient-derived organoids identify an apico-basolateral polarity switch associated with survival in colorectal cancer

Autor: Charlotte Canet-Jourdan, Diane-Laure Pagès, Clémence Nguyen-Vigouroux, Jérôme Cartry, Olivier Zajac, Christophe Desterke, Jean-Baptiste Lopez, Emie Gutierrez-Mateyron, Nicolas Signolle, Julien Adam, Joel Raingeaud, Mélanie Polrot, Patrick Gonin, Jacques R. R. Mathieu, Sylvie Souquere, Gerard Pierron, Maximiliano Gelli, Peggy Dartigues, Michel Ducreux, Valeria Barresi, Fanny Jaulin
Přispěvatelé: Dynamique des cellules tumorales (UMR1279), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Institut National de la Santé et de la Recherche Médicale (INSERM), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Physiologie et physiopathologie des rétrovirus endogènes et infectieux (RETRO-ENDO), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de chirurgie viscérale [Gustave Roussy], Département de biologie et pathologie médicales [Gustave Roussy], Département de médecine oncologique [Gustave Roussy], Università degli studi di Verona = University of Verona (UNIVR), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), raingeaud, joel
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Cell Science
Journal of Cell Science, 2022, 135 (14), pp.jcs259256. ⟨10.1242/jcs.259256⟩
ISSN: 0021-9533
1477-9137
Popis: The metastatic progression of cancer remains a major issue in patient treatment. However, the molecular and cellular mechanisms underlying this process remain unclear. Here, we use primary explants and organoids from patients harboring mucinous colorectal carcinoma (MUC CRC), a poor-prognosis histological form of digestive cancer, to study the architecture, invasive behavior and chemoresistance of tumor cell intermediates. We report that these tumors maintain a robust apico-basolateral polarity as they spread in the peritumoral stroma or organotypic collagen-I gels. We identified two distinct topologies – MUC CRCs either display a conventional ‘apical-in’ polarity or, more frequently, harbor an inverted ‘apical-out’ topology. Transcriptomic analyses combined with interference experiments on organoids showed that TGFβ and focal adhesion signaling pathways are the main drivers of polarity orientation. Finally, we show that the apical-out topology is associated with increased resistance to chemotherapeutic treatments in organoids and decreased patient survival in the clinic. Thus, studies on patient-derived organoids have the potential to bridge histological, cellular and molecular analyses to decrypt onco-morphogenic programs and stratify cancer patients. This article has an associated First Person interview with the first author of the paper.
Databáze: OpenAIRE
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