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基质金属蛋白酶9(MMP9)在神经胶质瘤中的高表达会影响细胞增殖,并与患者生存率相关。

High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates.

作者信息

Xue Qiang, Cao Li, Chen Xiao-Yan, Zhao Jing, Gao Liang, Li San-Zhong, Fei Zhou

机构信息

Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

Department of Human Resources, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

出版信息

Oncol Lett. 2017 Mar;13(3):1325-1330. doi: 10.3892/ol.2017.5567. Epub 2017 Jan 4.

Abstract

Human gliomas are a heterogeneous group of primary malignant brain tumors, which most commonly occur in the central nervous system of children and adults. Previous studies have suggested a prognostic role of matrix metalloproteinase 9 (MMP9) in glioma, however, the frequency and significance of the protein expression of MMP9 in glioma remain to be fully elucidated. In the present study, the expression of MMP9 was detected by reverse transcription-quantitative polymerase chain reaction (qPCR), western blotting and immunohistochemical staining. MTT and colony-forming assays were used to detect the role of MMP9 in the proliferation of glioma cells. MMP9 copy numbers in glioma were examined using qPCR. The results indicated that the expression level of MMP9 was significantly increased in glioma and was associated with World Health Organization (WHO) glioma grades. The high expression of MMP9 in tissues was an independent predictor of survival rates in patients with WHO grade III tumors. The overexpression of MMP9 promoted cell growth and induced a significant increase in clonogenic potential in U87 glioblastoma cell lines. These experimental data suggested that the overexpression of MMP9 in glioblastoma cells may occur primarily through an increase in gene copy number. The results of the present study suggested that the overexpression of MMP9 may be necessary for the transition to the more aggressive phenotype typical of WHO grade III gliomas, suggesting the likely involvement of the MMP9 gene in gliomagenesis and disease progression.

摘要

人类胶质瘤是一组异质性原发性恶性脑肿瘤,最常见于儿童和成人的中枢神经系统。先前的研究表明基质金属蛋白酶9(MMP9)在胶质瘤中具有预后作用,然而,MMP9在胶质瘤中的蛋白表达频率和意义仍有待充分阐明。在本研究中,通过逆转录定量聚合酶链反应(qPCR)、蛋白质印迹法和免疫组织化学染色检测MMP9的表达。采用MTT和集落形成试验检测MMP9在胶质瘤细胞增殖中的作用。使用qPCR检测胶质瘤中的MMP9拷贝数。结果表明,MMP9的表达水平在胶质瘤中显著升高,并且与世界卫生组织(WHO)胶质瘤分级相关。MMP9在组织中的高表达是WHO III级肿瘤患者生存率的独立预测指标。MMP9的过表达促进了细胞生长,并导致U87胶质母细胞瘤细胞系的克隆形成潜力显著增加。这些实验数据表明,胶质母细胞瘤细胞中MMP9的过表达可能主要通过基因拷贝数的增加而发生。本研究结果表明,MMP9的过表达可能是向WHO III级胶质瘤典型的更具侵袭性表型转变所必需的,提示MMP9基因可能参与胶质瘤的发生和疾病进展。

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