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Glutamine synthetase functions as a negative growth regulator in glioma

  • Laboratory Investigation
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Abstract

Our recent study demonstrated that glutamine synthetase (GS) may not only serve as a glutamate-converting enzyme in glial cells, but may also function as a regulator of astrocyte migration after injury. In this report, we showed that GS expression increased in cultured rat C6 glioma cells that underwent long-term serially propagation. The stable overexpression of GS in C6 glioma cells resulted in growth arrest and motility suppression; however the stable knockdown of GS resulted in motility enhancement. In correlation with cell aggregation, N-cadherin levels increased at sites of cell–cell contact in C6 cells overexpressing GS, and decreased in C6 cells with stable GS knockdown; total N-cadherin expression levels remained unchanged in these cells. In addition, levels of p21, a potent cyclin-dependent kinase inhibitor, increased, while cyclin D1 levels decreased in C6 cells overexpressing GS. Our additional studies showed that N-cadherin-mediated cell–cell contacts were implicated in GS-induced cell growth arrest and impairment of cell migration, as evidenced by the inhibition of GS on cell growth and motility by the neutralizing anti-N-cadherin monoclonal antibody (GC-4 mAb). Collectively, these observations suggest a novel mechanism of growth regulation by GS that involves N-cadherin mediated cell–cell contact.

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Acknowledgments

This work was supported by a Natural Science Foundation of China (NFSC) grant (81000527, 81100547); Natural Science Foundation of Jiangsu Province (NFSJS) grant (BK2010159); Science and Technology Development Program of Huadong Sanitarium (201001). The authors thank the International Science Editing Company for their language editing.

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Authors and Affiliations

  1. Department of Clinical Laboratory Science, Wuxi People’s Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People’s Republic of China

    Ying Yin, Bin Zhang, Ping Xie, Weizhen Qiao & Jian Zou

  2. Wuxi Clinical Science Research Institute, Wuxi, 214023, People’s Republic of China

    Ying Yin, Jie Xiang, Bin Zhang, Ping Xie, Weizhen Qiao & Jian Zou

  3. Department of Laboratory Medicine, Wuxi People’s Hospital of Nanjing Medical University, Wuxi, 214023, People’s Republic of China

    Weifeng Sun

  4. Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA

    Lingxiao Deng

  5. Department of Clinical Laboratory Science, Shanghai Huadong Sanitarium, 67 Jingyuan Road, Wuxi, 214065, Jiangsu, People’s Republic of China

    Chunxing Liu

Authors
  1. Ying Yin
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  2. Weifeng Sun
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  3. Jie Xiang
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  4. Lingxiao Deng
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  5. Bin Zhang
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  6. Ping Xie
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  7. Weizhen Qiao
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  8. Jian Zou
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  9. Chunxing Liu
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Corresponding authors

Correspondence to Jian Zou or Chunxing Liu.

Additional information

Ying Yin, Weifeng Sun, and Jie Xiang contributed equally to this study.

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Yin, Y., Sun, W., Xiang, J. et al. Glutamine synthetase functions as a negative growth regulator in glioma. J Neurooncol 114, 59–69 (2013). https://doi.org/10.1007/s11060-013-1168-5

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  • DOI: https://doi.org/10.1007/s11060-013-1168-5

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