Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, China.
PLoS One. 2019 Jan 29;14(1):e0211501. doi: 10.1371/journal.pone.0211501. eCollection 2019.
Gliomas are the most common malignant tumors of the brain and are characteristic of severe migration and invasion. Glial cell line-derived neurotrophic factor (GDNF) promotes glioma development process. However, the regulatory mechanisms of promoting occurrence and development of glioma have not yet been clearly elucidated. In the present study, the mechanism by which GDNF promotes glioma cell migration and invasion through regulating the dispersion and location of the Golgi apparatus (GA) is described. Following GDNF treatment, a change in the volume and position of GA was observed. The stack area of the GA was enlarged and it was more concentrated near the nucleus. Golgin-160 and Golgi microtubule-associated protein 210 (GMAP210) were identified as target molecules regulating GA positioning. In the absence of either golgin-160 or GMAP210 using lentivirus, the migration and invasion of U251 cells were decreased, while it was increased following GDNF. It was also found that the GA was decreased in size and dispersed following golgin-160 or GMAP210 knockdown, as determined by GA green fluorescence assay. Once GDNF was added, the above phenomenon would be twisted, and the concentrated location and volume of the GA was restored. In combination, the present data suggested that the regulation of the position and size of the GA by golgin-160 and GMAP210 play an important role in U251 cell migration and invasion.
神经胶质瘤是最常见的脑恶性肿瘤，其特征是严重的迁移和侵袭。胶质细胞源性神经营养因子（GDNF）促进神经胶质瘤的发生发展。然而，促进神经胶质瘤发生和发展的调节机制尚未阐明。本研究描述了 GDNF 通过调节高尔基体（GA）的分散和位置来促进神经胶质瘤细胞迁移和侵袭的机制。GDNF 处理后，观察到 GA 的体积和位置发生变化。GA 的堆叠面积增大，更集中在核附近。高尔基 160（Golgin-160）和高尔基体微管相关蛋白 210（GMAP210）被鉴定为调节 GA 定位的靶分子。使用慢病毒敲低 golgin-160 或 GMAP210 时，U251 细胞的迁移和侵袭减少，而加入 GDNF 后则增加。通过 GA 绿色荧光测定也发现，敲低 golgin-160 或 GMAP210 后 GA 减小且分散，一旦加入 GDNF，GA 集中的位置和体积就会恢复。综合来看，这些数据表明，golgin-160 和 GMAP210 对 GA 的位置和大小的调节在 U251 细胞迁移和侵袭中起重要作用。
