1. CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma
- Author
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Julie Giraud, Lornella Seeneevassen, Benoit Rousseau, Damien Bouriez, Elodie Sifré, Alban Giese, Tra Ly Nguyen, Camille Tiffon, Yannick Lippi, Lamia Azzi-Martin, Julie Pannequin, Armelle Ménard, Emilie Bessède, Cathy Staedel, Francis Mégraud, Geneviève Belleannée, Philippe Lehours, Caroline Gronnier, Pierre Dubus, Christine Varon, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, French ‘Institut National du Cancer’ (PLBio INCa, grant number 2014-152), La Ligue contre le Cancer (C Tiffon PhD salary, regional research grants comité Dordogne grant number R17013GG and comité Gironde grant number GM/12.17/37), UFR des sciences médicales Univ. Bordeaux (J Giraud and D Bouriez financial support), French ministry of national education, research and technologies (L Seeneevassen PhD salary)., and LESUR, Hélène
- Subjects
[SDV] Life Sciences [q-bio] ,Cancer Research ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Oncology ,Cancer stem cells ,Metastasis initiating cells ,[SDV]Life Sciences [q-bio] ,Gastroenterology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,General Medicine ,CD44 variant ,Epithelial-mesenchymal transition ,Gastric cancer - Abstract
Background Cancer stem cells (CSCs) are at the origin of tumour initiation and progression in gastric adenocarcinoma (GC). However, markers of metastasis-initiating cells remain unidentified in GC. In this study, we characterized CD44 variants expressed in GC and evaluated the tumorigenic and metastatic properties of CD44v3+ cells and their clinical significance in GC patients. Methods Using GC cell lines and patient-derived xenografts, we evaluated CD44+ and CD44v3+ GC cells molecular signature and their tumorigenic, chemoresistance, invasive and metastatic properties, and expression in patients-derived tissues. Results CD44v3+ cells, which represented a subpopulation of CD44+ cells, were detected in advanced preneoplastic lesions and presented CSCs chemoresistance and tumorigenic properties in vitro and in vivo. Molecular and functional analyses revealed two subpopulations of gastric CSCs: CD44v3+ CSCs with an epithelial-mesenchymal transition (EMT)-like signature, and CD44+/v3– CSCs with an epithelial-like signature; both were tumorigenic but CD44v3+ cells showed higher invasive and metastatic properties in vivo. CD44v3+ cells detected in the primary tumours of GC patients were associated with a worse prognosis. Conclusion CD44v3 is a marker of a subpopulation of CSCs with metastatic properties in GC. The identification of metastasis-initiating cells in GC represents a major advance for further development of anti-metastatic therapeutic strategies.
- Published
- 2022