{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:22:16Z","timestamp":1791555736436,"version":"4.3.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cancerop\u00f4le Ile-de-France","award":["2021-1-EMERG-43"],"award-info":[{"award-number":["2021-1-EMERG-43"]}]},{"DOI":"10.13039\/501100023479","name":"CRIS Cancer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100023479","id-type":"DOI","asserted-by":"crossref"}]},{"name":"La Marche de l\u2019Ecureuil"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diffuse midline gliomas (DMG) are pediatric tumors with negligible 2-year survival after diagnosis characterized by their ability to infiltrate the central nervous system. In the hope of controlling the local growth and slowing the disease, all patients receive radiotherapy. However, distant progression occurs frequently in DMG patients. Current clues as to what causes tumor infiltration circle mainly around the tumor microenvironment, but there are currently no known determinants to predict the degree of invasiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we use patient-derived glioma stem cells (GSCs) to create patient-specific 3D avatars to model interindividual invasion and elucidate the cellular supporting mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that GSC models in 3D mirror the invasive behavior of the parental tumors, thus proving the ability of DMG to infiltrate as an autonomous characteristic of tumor cells. Furthermore, we distinguished 2 modes of migration, mesenchymal and ameboid-like, and associated the ameboid-like modality with GSCs derived from the most invasive tumors. Using transcriptomics of both organoids and primary tumors, we further characterized the invasive ameboid-like tumors as oligodendrocyte progenitor-like, with highly contractile cytoskeleton and reduced adhesion ability driven by crucial over-expression of bone morphogenetic pathway 7 (BMP7). Finally, we deciphered MEK, ERK, and Rho\/ROCK kinases activated downstream of the BMP7 stimulation as actionable targets controlling tumor cell motility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings identify 2 new therapeutic avenues. First, patient-derived GSCs represent a predictive tool for patient stratification in order to adapt irradiation strategies. Second, autocrine and short-range BMP7-related signaling becomes a druggable target to prevent DMG spread and metastasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noad161","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:29:08Z","timestamp":1693823348000},"page":"553-568","source":"Crossref","is-referenced-by-count":34,"title":["Diffuse midline glioma invasion and metastasis rely on cell-autonomous signaling"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-0757","authenticated-orcid":false,"given":"Marco","family":"Bruschi","sequence":"first","affiliation":[{"name":"Inserm U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, Gustave Roussy, Universit\u00e9 Paris-Saclay , Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia","family":"Midjek","sequence":"additional","affiliation":[{"name":"Inserm U1279, Gustave Roussy Institute, Universit\u00e9 Paris-Saclay , Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassine","family":"Ajlil","sequence":"additional","affiliation":[{"name":"Inserm U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, Gustave Roussy, Universit\u00e9 Paris-Saclay , Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Vairy","sequence":"additional","affiliation":[{"name":"Inserm U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, Gustave Roussy, Universit\u00e9 Paris-Saclay , Villejuif , France"},{"name":"D\u00e9partement de Canc\u00e9rologie de l\u2019Enfant et de l\u2019Adolescent, Gustave Roussy, Universit\u00e9 Paris-Saclay , Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Lancien","sequence":"additional","affiliation":[{"name":"Inserm U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, Gustave Roussy, Universit\u00e9 Paris-Saclay , Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Ghermaoui","sequence":"additional","affiliation":[{"name":"Inserm U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, Gustave Roussy, Universit\u00e9 Paris-Saclay , Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kergrohen","sequence":"additional","affiliation":[{"name":"Inserm U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, Gustave Roussy, Universit\u00e9 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Oliveira","family":"de Biagi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Boston Children\u2019s Cancer and Blood Disorders Center , Boston , USA"},{"name":"Broad Institute of MIT and Harvard , Cambridge , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilon","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Boston Children\u2019s Cancer and Blood Disorders Center , Boston , USA"},{"name":"Broad Institute of MIT and Harvard , Cambridge , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariella G","family":"Filbin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Boston Children\u2019s Cancer and Blood Disorders Center , Boston , USA"},{"name":"Broad Institute of MIT and Harvard , Cambridge , 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Necker Enfants Malades Hospital, APHP, Universit\u00e9 Paris Cit\u00e9 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnault","family":"Tauziede-Espariat","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne Hospital , Paris France"},{"name":"Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR 1266, INSERM, IMA-BRAIN, Universit\u00e9 de Paris , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Varlet","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne Hospital , Paris France"},{"name":"Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR 1266, INSERM, IMA-BRAIN, Universit\u00e9 de Paris , Paris , 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