Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China.
J Neurooncol. 2013 Aug;114(1):59-69. doi: 10.1007/s11060-013-1168-5. Epub 2013 Jun 19.
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.
我们最近的研究表明，谷氨酰胺合成酶（GS）不仅可以作为神经胶质细胞中谷氨酸转化酶，而且可能在损伤后作为星形胶质细胞迁移的调节剂。在本报告中，我们表明，在长期连续传代培养的大鼠 C6 神经胶质瘤细胞中，GS 表达增加。GS 在 C6 神经胶质瘤细胞中的稳定过表达导致生长停滞和运动抑制；然而，GS 的稳定敲低导致运动增强。与细胞聚集相关，在过表达 GS 的 C6 细胞中，N-钙粘蛋白水平在细胞-细胞接触部位增加，而在稳定敲低 GS 的 C6 细胞中，N-钙粘蛋白水平降低；这些细胞中的总 N-钙粘蛋白表达水平保持不变。此外，在过表达 GS 的 C6 细胞中，细胞周期蛋白依赖性激酶抑制剂 p21 的水平增加，而 cyclin D1 水平降低。我们的进一步研究表明，N-钙粘蛋白介导的细胞-细胞接触参与了 GS 诱导的细胞生长停滞和迁移受损，这一点可以通过中和抗 N-钙粘蛋白单克隆抗体（GC-4 mAb）抑制 GS 对细胞生长和运动的作用得到证明。综上所述，这些观察结果表明了 GS 通过 N-钙粘蛋白介导的细胞-细胞接触来调节细胞生长的新机制。
