Journal
ONCOGENE
Volume 28, Issue 23, Pages 2266-2275Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.76
Keywords
glioma; cell of origin; neural stem cell; oligodendrocyte progenitor cell; glial cell; PDGF
Funding
- Swedish Cancer Society
- Swedish Research Council
- Association for International Cancer Research
- Lars Hiertas Minne
- Jeansson's Foundation
- Magn. Bergvall's Foundation
- Ake Wiberg's Foundation
- Department of Genetics and Pathology
- Medical Faculty of Uppsala University
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Gliomas are primary brain tumors mainly affecting adults. The cellular origin is unknown. The recent identification of tumor-initiating cells in glioma, which share many similarities with normal neural stem cells, has suggested the cell of origin to be a transformed neural stem cell. In previous studies, using the RCAS/tv-a mouse model, platelet-derived growth factor B (PDGF-B)induced gliomas have been generated from nestin or glial fibrillary acidic protein-expressing cells, markers of neural stem cells. To investigate if committed glial progenitor cells could be the cell of origin for glioma, we generated the Ctv-a mouse where tumor induction would be restricted to myelinating oligodendrocyte progenitor cells (OPCs) expressing 2',3'-cyclic nucleotide 3'-phosphodiesterase. We showed that PDGF-B transfer to OPCs could induce gliomas with an incidence of 33%. The majority of tumors resembled human WHO grade II oligodendroglioma based on close similarities in histopathology and expression of cellular markers. Thus, with the Ctv-a mouse we have showed that the cell of origin for glioma may be a committed glial progenitor cell. Oncogene (2009) 28, 2266-2275; doi: 10.1038/onc.2009.76; published online 27 April 2009
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