Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors.

Autor: Andersen MS; Department of Neurosurgery, Odense University Hospital, J. B. Winsløvs Vej 4, Odense C, 5000, Denmark. Mikkel.c.schou.andersen@rsyd.dk.; Department of Clinical Research, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark. Mikkel.c.schou.andersen@rsyd.dk.; BRIDGE (Brain Research ‑ Inter Disciplinary Guided Excellence), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark. Mikkel.c.schou.andersen@rsyd.dk., Halle B; Department of Neurosurgery, Odense University Hospital, J. B. Winsløvs Vej 4, Odense C, 5000, Denmark.; Department of Clinical Research, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark.; BRIDGE (Brain Research ‑ Inter Disciplinary Guided Excellence), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark., Wirenfeldt M; BRIDGE (Brain Research ‑ Inter Disciplinary Guided Excellence), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.; Department of Pathology and Molecular Biology, Hospital South West Jutland, Finsensgade 35, Esbjerg, 6700, Denmark.; Department of Regional Health Research, University of Southern Denmark, Campusvej 55, Odense M, Denmark., Petersen JK; Department of Pathology, Odense University Hospital, J. B. Winsløwsvej 15, Odense C, 5000, Denmark., Møller MW; Department of Neurosurgery, Odense University Hospital, J. B. Winsløvs Vej 4, Odense C, 5000, Denmark.; Department of Clinical Research, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark.; BRIDGE (Brain Research ‑ Inter Disciplinary Guided Excellence), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark., Jurmeister P; Institute of Pathology, Ludwig Maximilians University Hospital Munich, Thalkirchner Str. 36, 80337, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Olsen BB; Department of Clinical Research, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark.; Department of Nuclear Medicine, Odense University Hospital, J. B. Winsløvs Vej 4, Odense C, 5000, Denmark.; Department of Surgical Pathology, Zealand University Hospital, Sygehusvej 10, Roskilde, 4000, Denmark., Kristensen BW; Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej 5, Copenhagen N, 2200, Denmark.; Department of Pathology, The Bartholin Institute, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, 2100, Denmark., Boldt H; Department of Clinical Research, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark.; Department of Pathology, Odense University Hospital, J. B. Winsløwsvej 15, Odense C, 5000, Denmark., Pedersen CB; Department of Neurosurgery, Odense University Hospital, J. B. Winsløvs Vej 4, Odense C, 5000, Denmark.; Department of Clinical Research, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark.; BRIDGE (Brain Research ‑ Inter Disciplinary Guided Excellence), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark., Mathiesen T; Department of Neurosurgery, Rigshospitalet, and Copenhagen University, Blegdamsvej 9, Copenhagen, 2100, Denmark., Poulsen FR; Department of Neurosurgery, Odense University Hospital, J. B. Winsløvs Vej 4, Odense C, 5000, Denmark.; Department of Clinical Research, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark.; BRIDGE (Brain Research ‑ Inter Disciplinary Guided Excellence), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Dec 30; Vol. 14 (1), pp. 31933. Date of Electronic Publication: 2024 Dec 30.
DOI: 10.1038/s41598-024-83456-7
Abstrakt: Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation. Hence, there is a need for meningioma models with high translational value for understanding pathophysiology and tests of possible medical treatments. Resemblance between models and clinical meningiomas should be optimized with respect to morphology, immunohistochemistry and epigenetic factors, which we aimed to do. Third passage primary patient-derived benign meningiomas were implanted intracranially in athymic nude rats. The animals were euthanized after three months. We found intra- and intertumoral variability in terms of tumor take rate (79.5% for superficially implanted cells and 25% for deeply implanted cells) and xenograft sizes. There were close resemblance between primary tumors and xenografts in morphology and immunohistochemistry. Furthermore, we performed DNA-methylation using the EPIC 850 K array on three pairs of primary tumors and xenografts. Copy number variation profiles and correlation plots on CpGs showed a high degree of similarities between primary tumors and corresponding xenografts. On differential methylation analysis, most probes were insignificant (866,074), 25 were hypermethylated, and 382 were hypomethylated, where no significant differentially methylated regions were revealed.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study was approved by the Regional Committees on Health Research Ethics for Southern Denmark (S-20190105). All participants signed consent forms. The animal protocol was submitted to and approved (29th August 2019) by the Danish Animal Experiments Inspectorate (2019-15-0201-00195). The full approved protocol (in Danish) can be provided upon reasonable request. Consent for publication: All patients involved in the project have signed a regionally approved consent form.
(© 2024. The Author(s).)
Databáze: MEDLINE
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