Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma

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Abstract

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 theCtv-amouse 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 theCtv-amouse 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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