Proteomic identification of glutamine synthetase as a differential marker for oligodendrogliomas and astrocytomas: Laboratory investigation

Zhengping Zhuang, Meng Qi, Jie Li, Hiroaki Okamoto, David S. Xu, Rajiv R. Iyer, Jie Lu, Chunzhang Yang, Robert J. Weil, Alexander Vortmeyer, Russell R. Lonser

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Object. Astrocytomas and oligodendrogliomas are primary CNS tumors that remain a challenge to differentiate histologically because of their morphological variability and because there is a lack of reliable differential diagnostic markers. To identify proteins that are differentially expressed between astrocytomas and oligodendrogliomas, the authors analyzed the proteomic expression patterns and identified uniquely expressed proteins in these neoplasms. Methods. Proteomes of astrocytomas and oligodendrogliomas were analyzed using 2D gel electrophoresis and subsequent computerized gel analysis to detect differentially expressed proteins. The proteins were identified using high-performance liquid chromatography accompanied by tandem mass spectrometry. To determine the role of the differentially expressed proteins in astrocytes, undifferentiated glial cell cultures were treated with dibutyryl-cyclic adenosine monophosphate (cAMP). Results. Two-dimensional gel electrophoresis revealed that glutamine synthetase was differentially expressed in astrocytomas and oligodendrogliomas. Western blot and immunohistochemical analyses confirmed the increased expression of glutamine synthetase in astrocytomas compared with oligodendrogliomas. Whereas glutamine synthetase expression was demonstrated across all grades of astrocytomas (Grade II-IV [15 tumors]) and oligoastrocytomas (4 tumors), it was expressed in only 1 oligodendroglioma (6% [16 tumors]). Treatment of undifferentiated glial cell cultures with dibutyryl-cAMP resulted in astrocyte differentiation that was associated with increased levels of glial fibrillary acidic protein and glutamine synthetase. Conclusions. These data indicate that glutamine synthetase expression can be used to distinguish astrocytic from oligodendroglial tumors and may play a role in the pathogenesis of astrocytomas.

Original languageEnglish (US)
Pages (from-to)789-795
Number of pages7
JournalJournal of neurosurgery
Volume115
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • 2D gel electrophoresis
  • Astrocytoma
  • Glutamine synthetase
  • Mass spectrometry
  • Oligodendroglioma
  • Oncology
  • Proteomics

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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