{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:05:51Z","timestamp":1792663551944,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Pediatric high-grade gliomas (pHGGs) are facing a very dismal prognosis and representative pre-clinical models are needed for new treatment strategies. Here, we examined the relevance of collecting functional, genomic, and metabolomics data to validate patient-derived models in a hypoxic microenvironment. Methods: From our biobank of pediatric brain tumor-derived models, we selected 11 pHGGs driven by the histone H3.3K28M mutation. We compared the features of four patient tumors to their paired cell lines and mouse xenografts using NGS (next generation sequencing), aCGH (array comparative genomic hybridization), RNA sequencing, WES (whole exome sequencing), immunocytochemistry, and HRMAS (high resolution magic angle spinning) spectroscopy. We developed a multicellular in vitro model of cell migration to mimic the brain hypoxic microenvironment. The live cell technology Incucyte\u00a9 was used to assess drug responsiveness in variable oxygen conditions. Results: The concurrent 2D and 3D cultures generated from the same tumor sample exhibited divergent but complementary features, recreating the patient intra-tumor complexity. Genomic and metabolomic data described the metabolic changes during pHGG progression and supported hypoxia as an important key to preserve the tumor metabolism in vitro and cell dissemination present in patients. The neurosphere features preserved tumor development and sensitivity to treatment. Conclusion: We proposed a novel multistep work for the development and validation of patient-derived models, considering the immature and differentiated content and the tumor microenvironment of pHGGs.<\/jats:p>","DOI":"10.3390\/cancers11121875","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T10:57:27Z","timestamp":1574765847000},"page":"1875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Hypoxic Environment and Paired Hierarchical 3D and 2D Models of Pediatric H3.3-Mutated Gliomas Recreate the Patient Tumor Complexity"],"prefix":"10.3390","volume":"11","author":[{"given":"Anne-Florence","family":"Blandin","sequence":"first","affiliation":[{"name":"Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epid\u00e9miologie, University of Strasbourg, 3 avenue Moli\u00e8re, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Durand","sequence":"additional","affiliation":[{"name":"Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epid\u00e9miologie, University of Strasbourg, 3 avenue Moli\u00e8re, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Litzler","sequence":"additional","affiliation":[{"name":"Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epid\u00e9miologie, University of Strasbourg, 3 avenue Moli\u00e8re, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Tripp","sequence":"additional","affiliation":[{"name":"Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epid\u00e9miologie, University of Strasbourg, 3 avenue Moli\u00e8re, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9ric","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epid\u00e9miologie, University of Strasbourg, 3 avenue Moli\u00e8re, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Ruhland","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Obrecht","sequence":"additional","affiliation":[{"name":"PCBIS Plate-forme de chimie biologique int\u00e9grative de Strasbourg, UMS 3286, CNRS, Universit\u00e9 de Strasbourg, Labex Medalis, 300 boulevard Sebastien Brant, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Keime","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, CNRS UMR 7104, Inserm U964, 1 rue Laurent Fries, 67400 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Fuchs","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets, Faculty of Pharmacy, 74 route du Rhin, 67401 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Reita","sequence":"additional","affiliation":[{"name":"Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epid\u00e9miologie, University of Strasbourg, 3 avenue Moli\u00e8re, 67000 Strasbourg, France"},{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets, Faculty of Pharmacy, 74 route du Rhin, 67401 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Lhermitte","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets, Faculty of Pharmacy, 74 route du Rhin, 67401 Illkirch, France"},{"name":"Pathology Department, University Hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"},{"name":"Centre de Ressources Biologiques, CRB, University Hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Coca","sequence":"additional","affiliation":[{"name":"Neurosurgery, University Hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Jones","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SW7 3RP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle Lelong","family":"Rebel","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets, Faculty of Pharmacy, 74 route du Rhin, 67401 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Villa","sequence":"additional","affiliation":[{"name":"PCBIS Plate-forme de chimie biologique int\u00e9grative de Strasbourg, UMS 3286, CNRS, Universit\u00e9 de Strasbourg, Labex Medalis, 300 boulevard Sebastien Brant, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izzie Jacques","family":"Namer","sequence":"additional","affiliation":[{"name":"PCBIS Plate-forme de chimie biologique int\u00e9grative de Strasbourg, UMS 3286, CNRS, Universit\u00e9 de Strasbourg, Labex Medalis, 300 boulevard Sebastien Brant, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Dontenwill","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets, Faculty of Pharmacy, 74 route du Rhin, 67401 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Guenot","sequence":"additional","affiliation":[{"name":"Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epid\u00e9miologie, University of Strasbourg, 3 avenue Moli\u00e8re, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Entz-Werle","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets, Faculty of Pharmacy, 74 route du Rhin, 67401 Illkirch, France"},{"name":"Pediatric Onco-Hematology Department, Pediatrics, University hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1002\/cncr.23741","article-title":"Brain tumor epidemiology: Consensus from the brain tumor epidemiology consortium","volume":"113","author":"Bondy","year":"2008","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1200\/JCO.2017.76.0611","article-title":"Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma","volume":"36","author":"Grill","year":"2018","journal-title":"J. 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