The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma

Sridevi Yadavilli, Joseph Scafidi, Oren J. Becher, Amanda M. Saratsis, Rebecca L. Hiner, Madhuri Kambhampati, Santi Mariarita, Tobey J. MacDonald, Kari Elise Codispoti, Suresh N. Magge, Jyoti K. Jaiswal, Roger J. Packer, Javad Nazarian

Research output: Contribution to journalArticle

Abstract

Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis and are poorly understood brain cancers. Receptor tyrosine kinases stabilized by neuron-glial antigen 2 (NG2) protein are known to induce gliomagenesis. Here, we investigated NG2 expression in a cohort of DIPG specimens (n= 50). We demonstrate NG2 expression in the majority of DIPG specimens tested and determine that tumors harboring histone 3.3 mutation express the highest NG2 levels. We further demonstrate that microRNA 129-2 (miR129-2) is downregulated and hypermethylated in human DIPGs, resulting in the increased expression of NG2. Treatment with 5-Azacytidine, a methyltransferase inhibitor, results in NG2 downregulation in DIPG primary tumor cells in vitro. NG2 expression is altered (symmetric segregation) in mitotic human DIPG and mouse tumor cells. These mitotic cells co-express oligodendrocyte (Olig2) and astrocyte (glial fibrillary acidic protein, GFAP) markers, indicating lack of terminal differentiation. NG2 knockdown retards cellular migration in vitro, while NG2 expressing neurospheres are highly tumorigenic in vivo, resulting in rapid growth of pontine tumors. NG2 expression is targetable in vivo using miR129-2 indicating a potential avenue for therapeutic interventions. This data implicates NG2 as a molecule of interest in DIPGs especially those with H3.3 mutation.

Original languageEnglish (US)
Pages (from-to)12141-12155
Number of pages15
JournalOncotarget
Volume6
Issue number14
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Glioma
Neuroglia
Pediatrics
Neurons
Antigens
MicroRNAs
Down-Regulation
Brain Stem Neoplasms
Azacitidine
Neoplasms
Mutation
Glial Fibrillary Acidic Protein
Oligodendroglia
Methyltransferases
Receptor Protein-Tyrosine Kinases
Brain Neoplasms
Astrocytes
Histones

Keywords

  • DIPG
  • Glioma
  • Histone 3
  • NG2
  • PDGF

ASJC Scopus subject areas

  • Oncology

Cite this

Yadavilli, S., Scafidi, J., Becher, O. J., Saratsis, A. M., Hiner, R. L., Kambhampati, M., ... Nazarian, J. (2015). The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma. Oncotarget, 6(14), 12141-12155. https://doi.org/10.18632/oncotarget.3716

The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma. / Yadavilli, Sridevi; Scafidi, Joseph; Becher, Oren J.; Saratsis, Amanda M.; Hiner, Rebecca L.; Kambhampati, Madhuri; Mariarita, Santi; MacDonald, Tobey J.; Codispoti, Kari Elise; Magge, Suresh N.; Jaiswal, Jyoti K.; Packer, Roger J.; Nazarian, Javad.

In: Oncotarget, Vol. 6, No. 14, 01.01.2015, p. 12141-12155.

Research output: Contribution to journalArticle

Yadavilli, S, Scafidi, J, Becher, OJ, Saratsis, AM, Hiner, RL, Kambhampati, M, Mariarita, S, MacDonald, TJ, Codispoti, KE, Magge, SN, Jaiswal, JK, Packer, RJ & Nazarian, J 2015, 'The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma', Oncotarget, vol. 6, no. 14, pp. 12141-12155. https://doi.org/10.18632/oncotarget.3716
Yadavilli S, Scafidi J, Becher OJ, Saratsis AM, Hiner RL, Kambhampati M et al. The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma. Oncotarget. 2015 Jan 1;6(14):12141-12155. https://doi.org/10.18632/oncotarget.3716
Yadavilli, Sridevi ; Scafidi, Joseph ; Becher, Oren J. ; Saratsis, Amanda M. ; Hiner, Rebecca L. ; Kambhampati, Madhuri ; Mariarita, Santi ; MacDonald, Tobey J. ; Codispoti, Kari Elise ; Magge, Suresh N. ; Jaiswal, Jyoti K. ; Packer, Roger J. ; Nazarian, Javad. / The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma. In: Oncotarget. 2015 ; Vol. 6, No. 14. pp. 12141-12155.
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