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

Oncogene volume 28, pages 2266–2275 (2009)Cite this article

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 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.

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Acknowledgements

We thank Michel Gravel for the mouse Cnp promoter DNA and Karin Forsberg-Nilsson for the pTG8 plasmid. This work was supported by grants from The Swedish Cancer Society, The Swedish Research Council, Association for International Cancer Research, Lars Hiertas Minne, Jeansson's Foundation, Magn. Bergvall's Foundation, Åke Wiberg's Foundation, the Department of Genetics and Pathology and the Medical Faculty of Uppsala University.

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  1. T Olofsson

    Present address: 3Current address: Department of Forensic Medicine, The National Board of Forensic Medicine, Uppsala, Sweden.,

Authors and Affiliations

  1. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    N Lindberg, M Kastemar, T Olofsson & L Uhrbom

  2. Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden

    A Smits

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Correspondence to L Uhrbom.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Lindberg, N., Kastemar, M., Olofsson, T. et al. Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma. Oncogene 28, 2266–2275 (2009). https://doi.org/10.1038/onc.2009.76

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