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Mouse models of pediatric supratentorial high-grade glioma reveal how cell-of-origin influences tumor development and phenotype
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. CSIR, Inst Genom & Integrat Biol, South Campus,Mathura Rd, New Delhi 110025, India. (Lene Uhrbom)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. (Lene Uhrbom)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. (Lene Uhrbom)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. (Lene Uhrbom)
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2017 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, no 3, 802-812 p.Article in journal (Refereed) Published
Abstract [en]

High-grade glioma (HGG) is a group of primary malignant brain tumors with dismal prognosis. Whereas adult HGG has been studied extensively, childhood HGG, a relatively rare disease, is less well-characterized. Here, we present two novel platelet-derived growth factor (PDGF)-driven mouse models of pediatric supratentorial HGG. Tumors developed from two different cells of origin reminiscent of neural stem cells (NSC) or oligodendrocyte precursor cells (OPC). Cross-species transcriptomics showed that both models are closely related to human pediatric HGG as compared with adult HGG. Furthermore, an NSC-like cell-of-origin enhanced tumor incidence, malignancy, and the ability of mouse glioma cells (GC) to be cultured under stem cell conditions as compared with an OPC-like cell. Functional analyses of cultured GC from these tumors showed that cells of NSC-like origin were more tumorigenic, had a higher rate of self-renewal and proliferation, and were more sensitive to a panel of cancer drugs compared with GC of a more differentiated origin. These two mouse models relevant to human pediatric supratentorial HGG propose an important role of the cell-of-origin for clinicopathologic features of this disease.

Place, publisher, year, edition, pages
2017. no 3, 802-812 p.
Keyword [en]
pediatric high-grade glioma, glioblastoma, mouse model, cell of origin, glioma stem cell
National Category
Cell and Molecular Biology
Research subject
Biomedical Laboratory Science
Identifiers
URN: urn:nbn:se:uu:diva-310215DOI: 10.1158/0008-5472.CAN-16-2482ISI: 000393194400020OAI: oai:DiVA.org:uu-310215DiVA: diva2:1055690
Funder
Swedish Cancer SocietySwedish Childhood Cancer FoundationSwedish Research CouncilSwedish Society for Medical Research (SSMF)
Available from: 2016-12-13 Created: 2016-12-13 Last updated: 2017-03-20Bibliographically approved

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Sreedharan, SmithaMaturi, Naga PrathyushaXie, YuanSundström, AndersJarvius, MalinLibard, SylwiaAlafuzoff, IrinaWeishaupt, HolgerFryknäs, MårtenLarsson, RolfSwartling, Fredrik J.Uhrbom, Lene
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Neuro-OncologyScience for Life Laboratory, SciLifeLabCancer Pharmacology and Computational MedicineDepartment of Immunology, Genetics and Pathology
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