Qin Jun-Jie, Wang Jun-Mei, Du Jiang, Zeng Chun, Han Wu, Li Zhi-Dong, Xie Jian, Li Gui-Lin
Department of Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China E-mail :
Asian Pac J Cancer Prev. 2014;15(22):9805-12. doi: 10.7314/apjcp.2014.15.22.9805.
Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or non- sense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin- suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.
根蛋白是ERM（埃兹蛋白-根蛋白-膜突蛋白）家族的成员之一，在细胞运动、侵袭和肿瘤进展中发挥重要作用。它在多种正常细胞和肿瘤细胞中表达，包括许多类型的上皮细胞和淋巴细胞。然而，其在胶质母细胞瘤中的功能仍不清楚。因此，在本研究中，首先检测了胶质母细胞瘤细胞中根蛋白基因的表达，然后用慢病毒介导的短发夹RNA（shRNA）方法对其进行抑制。我们发现胶质母细胞瘤U251细胞中根蛋白表达水平较高。根蛋白shRNA导致根蛋白基因表达下调，当将根蛋白沉默的细胞接种到裸鼠体内时，与空白对照细胞或无义shRNA细胞相比，肿瘤生长受到显著抑制。此外，肿瘤中的微血管密度显著降低。在根蛋白抑制的胶质母细胞瘤U251细胞中，血小板反应蛋白-1（TSP-1）和E-钙黏蛋白上调。相反，基质金属蛋白酶9（MMP9）下调。综上所述，我们的研究结果表明根蛋白参与了胶质母细胞瘤细胞的迁移和侵袭，并提示TSP-1、E-钙黏蛋白和MMP9是转移诱导因子。
