{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:26:14Z","timestamp":1791559574897,"version":"4.3.4"},"reference-count":96,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100021170","name":"Brain Tumour Research","doi-asserted-by":"publisher","award":["Hanemann"],"award-info":[{"award-number":["Hanemann"]}],"id":[{"id":"10.13039\/501100021170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Meningiomas are the most common intracranial brain tumours. These tumours are heterogeneous and encompass a wide spectrum of clinical aggressivity. Treatment options are limited to surgery and radiotherapy and have a risk of post-operative morbidities and radiation neurotoxicity, reflecting the need for new therapies. Three-dimensional (3D) patient-derived cell culture models have been shown to closely recapitulate in vivo tumour biology, including microenvironmental interactions and have emerged as a robust tool for drug development. Here, we established a novel easy-to-use 3D patient-derived meningioma spheroid model using a scaffold-free approach. Patient-derived meningioma spheroids were characterised and compared to patient tissues and traditional monolayer cultures by histology, genomics, and transcriptomics studies. Patient-derived meningioma spheroids closely recapitulated morphological and molecular features of matched patient tissues, including patient histology, genomic alterations, and components of the immune microenvironment, such as a CD68\u2009+\u2009and CD163\u2009+\u2009positive macrophage cell population. Comprehensive transcriptomic profiling revealed an increase in epithelial-to-mesenchymal transition (EMT) in meningioma spheroids compared to traditional monolayer cultures, confirming this model as a tool to elucidate EMT in meningioma. Therefore, as proof of concept study, we developed a treatment strategy to target EMT in meningioma. We found that combination therapy using the MER tyrosine kinase (MERTK) inhibitor UNC2025 and the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) effectively decreased meningioma spheroid viability and proliferation. Furthermore, we demonstrated this combination therapy significantly increased the expression of the epithelial marker E-cadherin and had a repressive effect on WHO grade 2-derived spheroid invasion, which is suggestive of a partial reversal of EMT in meningioma spheroids.<\/jats:p>","DOI":"10.1186\/s40478-023-01677-9","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T12:02:03Z","timestamp":1702641723000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A novel patient-derived meningioma spheroid model as a tool to study and treat epithelial-to-mesenchymal transition (EMT) in meningiomas"],"prefix":"10.1186","volume":"11","author":[{"given":"Laurien L.","family":"van de Weijer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Ercolano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Banton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathreena M.","family":"Kurian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1951-1025","authenticated-orcid":false,"given":"C. Oliver","family":"Hanemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"1677_CR1","doi-asserted-by":"publisher","first-page":"I2","DOI":"10.1093\/neuonc\/noy181","volume":"21","author":"F Nassiri","year":"2019","unstructured":"Nassiri F, Tabatabai G, Aldape K, Zadeh G (2019) Challenges and opportunities in meningiomas: recommendations from the International Consortium on Meningiomas. Neuro-Oncol 21:I2\u2013I3. https:\/\/doi.org\/10.1093\/neuonc\/noy181","journal-title":"Neuro-Oncol"},{"key":"1677_CR2","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-022-05301-y","author":"SH Torp","year":"2022","unstructured":"Torp SH, Solheim O, Skjulsvik AJ (2022) The WHO 2021 classification of central nervous system tumours: a practical update on what neurosurgeons need to know\u2014a minireview. 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