Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Br J Cancer. 2019 Apr;120(8):819-826. doi: 10.1038/s41416-019-0413-x. Epub 2019 Mar 14.
Glioblastoma multiforme (GBM), the most common brain malignancy in adults, is generally aggressive and incurable, even with multiple treatment modalities and agents. Filamins (FLNs) are a group of actin-binding proteins that regulate the actin cytoskeleton in cells. However, the role of FLNs in malignancies-particularly in GBM-is unclear.
The relation between FLNC expression and overall survival in GBM was evaluated by the Kaplan-Meier analysis using GBM patients from the Kagoshima University Hospital (n = 90) and data from the Cancer Genome Atlas (TCGA) (n = 153). To assess FLNC function in GBM, cell migration and invasion were examined with Transwell and Matrigel invasion assays using FLNC-overexpressing U251MG and LN299 GBM cells, and ShRNA-mediated FLNC knocked-down KNS81 and U87MG cells. The gelatin zymography assay was used to estimate matrix metalloproteinase (MMP) 2 activity.
In silico analysis of GBM patient data from TCGA and immunohistochemical analyses of clinical GBM specimens revealed that increased FLNC expression was associated with poor patient prognosis. FLNC overexpression in GBM cell lines was positively correlated with enhanced invasiveness, but not migration, and was accompanied by upregulation of MMP2.
FLNC is a potential therapeutic target and biomarker for GBM progression.
多形性胶质母细胞瘤（GBM）是成人中最常见的脑恶性肿瘤，即使采用多种治疗方式和药物，其侵袭性也很强，通常无法治愈。细丝蛋白（FLNs）是一组肌动蛋白结合蛋白，可调节细胞中的肌动蛋白细胞骨架。然而，FLNs 在恶性肿瘤中的作用——尤其是在 GBM 中——尚不清楚。
通过对来自鹿儿岛大学医院（n=90）的 GBM 患者和癌症基因组图谱（TCGA）（n=153）的数据进行 Kaplan-Meier 分析，评估 FLNC 表达与 GBM 患者总生存期之间的关系。为了评估 FLNC 在 GBM 中的功能，使用 Transwell 和 Matrigel 侵袭实验，用 FLNC 过表达的 U251MG 和 LN299 GBM 细胞，以及通过 ShRNA 介导的 FLNC 敲低的 KNS81 和 U87MG 细胞，检测细胞迁移和侵袭。使用明胶酶谱分析来评估基质金属蛋白酶（MMP）2 的活性。
对 TCGA 的 GBM 患者数据进行的计算机分析和对临床 GBM 标本的免疫组织化学分析表明，FLNC 表达增加与患者预后不良有关。GBM 细胞系中 FLNC 的过表达与侵袭性增强呈正相关，但与迁移无关，并且伴随着 MMP2 的上调。
FLNC 是 GBM 进展的潜在治疗靶点和生物标志物。
