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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
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Animals
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Avian Proteins / genetics
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Cell Proliferation / drug effects
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Cells, Cultured
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Chickens
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Genetic Vectors / genetics
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Glioma / genetics
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Glioma / metabolism
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Glioma / pathology*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Immunohistochemistry
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Mice
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Mice, Transgenic
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology*
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Oligodendroglia / cytology*
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Oligodendroglia / metabolism
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Phosphoric Diester Hydrolases / metabolism
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Platelet-Derived Growth Factor / genetics
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Platelet-Derived Growth Factor / metabolism
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Platelet-Derived Growth Factor / pharmacology
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor, Platelet-Derived Growth Factor alpha / metabolism
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Receptors, Virus / genetics
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Stem Cells / cytology*
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Stem Cells / metabolism
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Transfection
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Vimentin / metabolism
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Avian Proteins
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Platelet-Derived Growth Factor
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Receptors, Virus
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Tva receptor
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Vimentin
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Green Fluorescent Proteins
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Receptor, Platelet-Derived Growth Factor alpha
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Proto-Oncogene Proteins c-akt
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Phosphoric Diester Hydrolases
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2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
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CNP protein, human
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Cnp protein, mouse
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ras Proteins