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

14 Citations (Scopus)

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 1 2011
Externally publishedYes

Fingerprint

Oligodendroglioma
Glutamate-Ammonia Ligase
Astrocytoma
Proteomics
Electrophoresis, Gel, Two-Dimensional
Neoplasms
Neoplasm Proteins
Neuroglia
Astrocytes
Cyclic AMP
Proteins
Cell Culture Techniques
Glial Fibrillary Acidic Protein
Proteome
Glioblastoma
Tandem Mass Spectrometry
Western Blotting
Gels
High Pressure Liquid Chromatography

Keywords

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

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Proteomic identification of glutamine synthetase as a differential marker for oligodendrogliomas and astrocytomas : Laboratory investigation. / Zhuang, Zhengping; Qi, Meng; Li, Jie; Okamoto, Hiroaki; Xu, David S.; Iyer, Rajiv R.; Lu, Jie; Yang, Chunzhang; Weil, Robert J.; Vortmeyer, Alexander; Lonser, Russell R.

In: Journal of neurosurgery, Vol. 115, No. 4, 01.10.2011, p. 789-795.

Research output: Contribution to journalArticle

Zhuang, Zhengping ; Qi, Meng ; Li, Jie ; Okamoto, Hiroaki ; Xu, David S. ; Iyer, Rajiv R. ; Lu, Jie ; Yang, Chunzhang ; Weil, Robert J. ; Vortmeyer, Alexander ; Lonser, Russell R. / Proteomic identification of glutamine synthetase as a differential marker for oligodendrogliomas and astrocytomas : Laboratory investigation. In: Journal of neurosurgery. 2011 ; Vol. 115, No. 4. pp. 789-795.
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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.",
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T1 - Proteomic identification of glutamine synthetase as a differential marker for oligodendrogliomas and astrocytomas

T2 - Laboratory investigation

AU - Zhuang, Zhengping

AU - Qi, Meng

AU - Li, Jie

AU - Okamoto, Hiroaki

AU - Xu, David S.

AU - Iyer, Rajiv R.

AU - Lu, Jie

AU - Yang, Chunzhang

AU - Weil, Robert J.

AU - Vortmeyer, Alexander

AU - Lonser, Russell R.

PY - 2011/10/1

Y1 - 2011/10/1

N2 - 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.

AB - 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.

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KW - Astrocytoma

KW - Glutamine synthetase

KW - Mass spectrometry

KW - Oligodendroglioma

KW - Oncology

KW - Proteomics

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