State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
J Pathol. 2012 Feb;226(3):534-43. doi: 10.1002/path.3008. Epub 2011 Dec 5.
Stomatin-like protein 2 (STOML2), a member of the stomatin family, has been reported to be up-regulated in several types of human cancers. The clinical significance and biological role of STOML2 in gliomas remain largely unknown. Here, we describe the significantly up-regulated expression of STOML2 in glioma cell lines and glioma tissues at both the transcriptional and translational levels. Silencing endogenous STOML2 in glioma cells and primary glioma cells drastically reduced their migratory speed and invasive ability, associated with induction of matrix metallopeptidase 9 (MMP-9). We also demonstrated that knockdown of STOML2 significantly inhibited the transcriptional activity of NF-κB and repressed the expression levels of NF-κB target genes, including MMP-9. A luciferase reporter assay revealed that the impact of STOML2 on MMP-9 expression is NF-κB-dependent. Immunohistochemical analysis showed that the up-regulation of STOML2 was significantly correlated with the WHO histological grade of gliomas (p < 0.001). Patients with higher STOML2 expression levels had an overall shorter survival time, whereas patients with lower expression of STOML2 had a longer survival time. A multivariate analysis revealed that STOML2 expression might be an independent prognostic indicator for the survival of glioma patients. Taken together, our results suggest that overexpression of STOML2 is associated with glioma aggressiveness and may represent an independent prognostic factor for the outcome of glioma patients.
质膜突起蛋白 2（STOML2）是质膜突起家族的一个成员，已被报道在多种人类癌症中上调。STOML2 在神经胶质瘤中的临床意义和生物学作用在很大程度上尚不清楚。在这里，我们描述了 STOML2 在神经胶质瘤细胞系和神经胶质瘤组织中转录和翻译水平的显著上调表达。在神经胶质瘤细胞和原代神经胶质瘤细胞中沉默内源性 STOML2 会极大地降低其迁移速度和侵袭能力，同时诱导基质金属蛋白酶 9（MMP-9）。我们还证明，STOML2 的敲低显著抑制了 NF-κB 的转录活性，并抑制了 NF-κB 靶基因的表达水平，包括 MMP-9。荧光素酶报告基因检测表明，STOML2 对 MMP-9 表达的影响依赖于 NF-κB。免疫组织化学分析表明，STOML2 的上调与神经胶质瘤的 WHO 组织学分级显著相关（p<0.001）。STOML2 表达水平较高的患者总生存时间较短，而 STOML2 表达水平较低的患者生存时间较长。多变量分析显示，STOML2 表达可能是神经胶质瘤患者生存的独立预后指标。总之，我们的结果表明，STOML2 的过表达与神经胶质瘤的侵袭性有关，可能是神经胶质瘤患者预后的独立预后因素。
