Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
PLoS One. 2014 May 30;9(5):e98544. doi: 10.1371/journal.pone.0098544. eCollection 2014.
Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene in several solid tumors. However, the expression and function of BRMS1 in glioma have not been reported. In this study, we investigated whether BRMS1 play a role in glioma pathogenesis. Using the tissue microarray technology, we found that BRMS1 expression is significantly decreased in glioma compared with tumor adjacent normal brain tissue (P<0.01, χ(2) test) and reduced BRMS1 staining is associated with WHO stages (P<0.05, χ(2) test). We also found that BRMS1 was significantly downregulated in glioma cell lines compared to normal human astrocytes (P<0.01, χ(2) test). Furthermore, we demonstrated that BRMS1 overexpression inhibited glioma cell invasion by suppressing uPA, NF-κB, MMP-2 expression and MMP-2 enzyme activity. Moreover, our data showed that overexpression of BRMS1 inhibited glioma cell migration and adhesion capacity compared with the control group through the Src-FAK pathway. Taken together, this study suggested that BRMS1 has a role in glioma development and progression by regulating invasion, migration and adhesion activities of cancer cells.
乳腺癌转移抑制因子 1（BRMS1）是几种实体肿瘤中的转移抑制基因。然而，BRMS1 在神经胶质瘤中的表达和功能尚未被报道。在本研究中，我们研究了 BRMS1 是否在神经胶质瘤发病机制中发挥作用。使用组织微阵列技术，我们发现与肿瘤相邻的正常脑组织相比，BRMS1 在神经胶质瘤中的表达显著降低（P<0.01，卡方检验），并且 BRMS1 染色减少与 WHO 分期相关（P<0.05，卡方检验）。我们还发现 BRMS1 在神经胶质瘤细胞系中的表达明显低于正常人星形胶质细胞（P<0.01，卡方检验）。此外，我们证明 BRMS1 过表达通过抑制 uPA、NF-κB、MMP-2 表达和 MMP-2 酶活性抑制神经胶质瘤细胞侵袭。此外，与对照组相比，我们的数据表明 BRMS1 过表达通过 Src-FAK 通路抑制神经胶质瘤细胞迁移和黏附能力。综上所述，本研究表明 BRMS1 通过调节癌细胞的侵袭、迁移和黏附活性在神经胶质瘤的发生和发展中发挥作用。
