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PMID: 20651032 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Carcinogenesis ·Vol. 31 ·No. 10 ·2010-10-00 ·Pages 1718-25

Briançon-Marjollet A, Balenci L, Fernandez M, Estève F, Honnorat J, Farion R, Beaumont M, Barbier E, Rémy C, Baudier J

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.

MeSH Terms
Animals Antigens/analysis Brain Neoplasms/chemically induced,pathology Cell Differentiation Cell Line, Tumor Ethylnitrosourea/toxicity Neoplastic Stem Cells/chemistry,pathology Oligodendroglioma/chemically induced,pathology Proteoglycans/analysis Rats Rats, Sprague-Dawley ras GTPase-Activating Proteins/analysis
Chemicals
Antigens IQ motif containing GTPase activating protein 1 Proteoglycans chondroitin sulfate proteoglycan 4 ras GTPase-Activating Proteins Ethylnitrosourea
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Briançon-Marjollet Anne
INSERM U873, 38054 Grenoble, France.
Balenci Laurent
Fernandez Manuel
Estève François
Honnorat Jérôme
Farion Régine
Beaumont Marine
Barbier Emmanuel
Rémy Chantal
Baudier Jacques
References (47)
47 references, click to expand
  1. Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas.
    J Neurooncol. 2006 Jan;76(2):115-27 PMID: 16205963
  2. Cycling cells in the adult rat neocortex preferentially generate oligodendroglia.
    J Neurosci Res. 1999 Aug 15;57(4):435-46 PMID: 10440893
  3. IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme.
    Cancer Res. 2006 Sep 15;66(18):9074-82 PMID: 16982749
  4. Brain tumors in S100beta-v-erbB transgenic rats.
    J Neuropathol Exp Neurol. 2006 Dec;65(12):1111-7 PMID: 17146284
  5. Oligodendroglioma.
    Curr Treat Options Neurol. 2005 Jul;7(4):305-314 PMID: 15967093
  6. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo.
    Genes Dev. 2001 Aug 1;15(15):1913-25 PMID: 11485986
  7. Making a tumour's bed: glioblastoma stem cells and the vascular niche.
    Nat Rev Cancer. 2007 Oct;7(10):733-6 PMID: 17882276
  8. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.
    Nature. 2006 Dec 7;444(7120):756-60 PMID: 17051156
  9. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.
    J Cell Biol. 2003 Apr 14;161(1):169-86 PMID: 12682089
  10. Lack of replicative senescence in cultured rat oligodendrocyte precursor cells.
    Science. 2001 Feb 2;291(5505):868-71 PMID: 11157165
  11. Heterogeneity of NG2-expressing cells in the newborn mouse cerebellum.
    Dev Biol. 2005 Sep 15;285(2):409-21 PMID: 16084507
  12. N-ethyl-N-nitrosourea (ENU) increased brain mutations in prenatal and neonatal mice but not in the adults.
    Toxicol Sci. 2004 Sep;81(1):112-20 PMID: 15159527
  13. Nuclear expression of S100B in oligodendrocyte progenitor cells correlates with differentiation toward the oligodendroglial lineage and modulates oligodendrocytes maturation.
    Mol Cell Neurosci. 2004 Dec;27(4):453-65 PMID: 15555923
  14. Neuronal features of oligodendrogliomas--an ultrastructural and immunohistochemical study.
    Histopathology. 2007 Jun;50(7):887-96 PMID: 17543079
  15. Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus.
    Cancer Res. 1998 Dec 1;58(23):5275-9 PMID: 9850047
  16. Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses.
    J Neurosci. 2006 Jun 21;26(25):6781-90 PMID: 16793885
  17. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice.
    Nat Neurosci. 2008 Dec;11(12):1392-401 PMID: 18849983
  18. IQGAP1 regulates adult neural progenitors in vivo and vascular endothelial growth factor-triggered neural progenitor migration in vitro.
    J Neurosci. 2007 Apr 25;27(17):4716-24 PMID: 17460084
  19. Evaluation of ENU-induced gliomas in rats: nomenclature, immunochemistry, and malignancy.
    Toxicol Pathol. 2000 Jan-Feb;28(1):193-201 PMID: 10669007
  20. Identification of human brain tumour initiating cells.
    Nature. 2004 Nov 18;432(7015):396-401 PMID: 15549107
  21. Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development.
    J Neurosci. 2002 Feb 1;22(3):876-85 PMID: 11826117
  22. Genetic determinants of malignancy in a mouse model for oligodendroglioma.
    Cancer Res. 2003 Apr 1;63(7):1589-95 PMID: 12670909
  23. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells.
    Science. 2000 Sep 8;289(5485):1754-7 PMID: 10976069
  24. Mouse astrocytoma models: embryonic stem cell mediated transgenesis.
    J Neurooncol. 2001 Jul;53(3):289-96 PMID: 11718261
  25. Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas: implications for glioma histogenesis and biology.
    Glia. 2009 Apr 1;57(5):510-23 PMID: 18837053
  26. Isolation of immortalized, INK4a/ARF-deficient cells from the subventricular zone after in utero N-ethyl-N-nitrosourea exposure.
    J Neurosurg. 2005 Jan;102(1):98-108 PMID: 15658102
  27. NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS.
    Mol Cell Neurosci. 2003 Oct;24(2):476-88 PMID: 14572468
  28. Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma.
    Oncogene. 2009 Jun 11;28(23):2266-75 PMID: 19421151
  29. Expression of oligodendrocyte lineage genes in oligodendroglial and astrocytic gliomas.
    Acta Neuropathol. 2004 Mar;107(3):277-82 PMID: 14730454
  30. Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone.
    J Neurosci. 2004 Nov 17;24(46):10530-41 PMID: 15548668
  31. Oligodendrogliomas: clinical and genetic correlations.
    Curr Opin Neurol. 2001 Dec;14(6):705-10 PMID: 11723377
  32. Cancerous stem cells can arise from pediatric brain tumors.
    Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15178-83 PMID: 14645703
  33. Chemical induction of brain tumors in rats by nitrosoureas: molecular biology and neuropathology.
    Neurotoxicol Teratol. 1989 Nov-Dec;11(6):551-6 PMID: 2696875
  34. Magnetic resonance imaging of ethyl-nitrosourea-induced rat gliomas: a model for experimental therapeutics of low-grade gliomas.
    J Neurooncol. 2001 Jul;53(3):243-57 PMID: 11718257
  35. Expression of oligodendrocyte progenitor cell antigens by gliomas: implications for the histogenesis of brain tumors.
    Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10361-6 PMID: 10468613
  36. Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt.
    Cancer Res. 2002 Oct 1;62(19):5551-8 PMID: 12359767
  37. NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus.
    J Cell Biol. 2004 May 24;165(4):575-89 PMID: 15159421
  38. Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma.
    J Neuropathol Exp Neurol. 1995 Jan;54(1):91-5 PMID: 7815084
  39. A matter of identity: transcriptional control in oligodendrocytes.
    J Mol Neurosci. 2008 May;35(1):3-12 PMID: 18401762
  40. Characterization of N-nitrosourea-induced tumors of the nervous system; their prospective value for studies of neurocarcinogenesis and brain tumor therapy.
    Toxicol Pathol. 1990;18(1 Pt 2):186-92 PMID: 2195638
  41. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain.
    Nat Med. 2003 Apr;9(4):439-47 PMID: 12627226
  42. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma.
    Cancer Res. 2004 Oct 1;64(19):7011-21 PMID: 15466194
  43. Astrocytes give rise to oligodendrogliomas and astrocytomas after gene transfer of polyoma virus middle T antigen in vivo.
    Am J Pathol. 2000 Sep;157(3):1031-7 PMID: 10980141
  44. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice.
    Nat Genet. 2000 May;25(1):55-7 PMID: 10802656
  45. Expression of neuronal and glial markers in so-called oligodendroglial tumors induced by transplacental administration of ethyl-nitrosourea in the rat.
    Histol Histopathol. 1992 Oct;7(4):647-51 PMID: 1457988
  46. NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors?
    J Neurosci Res. 2000 Sep 1;61(5):471-9 PMID: 10956416
  47. Low-grade oligodendroglioma: current treatments and future hopes.
    Expert Rev Anticancer Ther. 2009 Nov;9(11):1651-61 PMID: 19895248
Article Info
Journal
Carcinogenesis
Abbr.
Carcinogenesis
ISSN
1460-2180
DOI
10.1093/carcin/bgq154
Published
2010-10-00
Epub
2010-00-22
Pages
1718-25
Language
English
Region
England
NLM ID
8008055
PMCID
PMC3308186
Subset
IM
External Links
PubMed source DOI: 10.1093/carcin/bgq154 PMC Full Text View journal details
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