NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis.: Brain precursor cells and gliomas

Anne Briançon-Marjollet 1 Laurent Balenci 1 Manuel Fernandez 2, 3 François Estève 2, 3 Jérôme Honnorat 4 Régine Farion 2 Marine Beaumont 2 Emmanuel Barbier 2 Chantal Rémy 2 Jacques Baudier 1, *
* Auteur correspondant
1 Transduction du signal : signalisation calcium, phosphorylation et inflammation
2 GIN - Grenoble Institut des Neurosciences
3 ESRF - European Synchrotron Radiation Facility
4 Neuro-oncologie et neuro-inflammation
Abstract : Gliomas are the most common primary brain tumor affecting human adults and remain a therapeutic challenge because cells of origin are still unknown. Here, we investigated the cellular origin of low-grade gliomas in a rat model based on transplacental exposure to N-ethyl-N-nitrosourea (ENU). Longitudinal magnetic resonance imaging coupled to immunohistological and immunocytochemical analyses were used to further characterize low-grade rat gliomas at different stages of evolution. We showed that early low-grade gliomas have characteristics of oligodendroglioma-like tumors and exclusively contain NG2-expressing slow dividing precursor cells, which express early markers of oligodendroglial lineage. These tumor-derived precursors failed to fully differentiate into oligodendrocytes and exhibited multipotential abilities in vitro. Moreover, a few glioma NG2+ cells are resistant to radiotherapy and may be responsible for tumor recurrence, frequently observed in humans. Overall, these findings suggest that transformed multipotent NG2 glial precursor cell may be a potential cell of origin in the genesis of rat ENU-induced oligodendroglioma-like tumors. This work may open up new perspectives for understanding biology of human gliomas.
keyword : Glial precursor Cancer stem cells Glioblastoma Oligodendroglioma NG2 neural progenitors
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Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), 2010, 31 (10), pp.1718-25. 〈10.1093/carcin/bgq154〉
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Anne Briançon-Marjollet, Laurent Balenci, Manuel Fernandez, François Estève, Jérôme Honnorat, et al.. NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis.: Brain precursor cells and gliomas. Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), 2010, 31 (10), pp.1718-25. 〈10.1093/carcin/bgq154〉. 〈inserm-00567905〉

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