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Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin
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. Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
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2017 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 18, no 4, 977-990 p.Article in journal (Refereed) Published
Abstract [en]

The identity of the glioblastoma (GBM) cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC) properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP)-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP) that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES) or 2,'3'-cyclic nucleotide 3'-phosphodiesterase (mGC3CNP)-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO) gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.

Place, publisher, year, edition, pages
2017. Vol. 18, no 4, 977-990 p.
Keyword [en]
cancer stem cell, cell of origin, central nervous system, drug response, glioblastoma, glioma, mouse model, neural stem cell, oligodendrocyte precursor cell, self-renewal
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-319084DOI: 10.1016/j.celrep.2017.01.003ISI: 000396474300013PubMedID: 28122246OAI: oai:DiVA.org:uu-319084DiVA: diva2:1086132
Funder
Swedish Cancer Society, 110363 140385 150628Swedish Research Council, 90283201 C0259101 B0310101 E0331401Swedish Childhood Cancer Foundation, PROJ11/057 PR2014-0143Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-04-10Bibliographically approved

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