Down-regulation of 67LR reduces the migratory activity of human glioma cells in vitro
Down-regulation of 67LR reduces the migratory activity of human glioma cells in vitro
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DOI：
10.1016/j.brainresbull.2009.04.019
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发表时间：
2009-08-14
影响因子：
3.8
通讯作者：
Ji, Y. H.
中科院分区：
文献类型：
--
作者：
Chen, F. X.;Qian, Y. R.;Ji, Y. H.
目的：胶质瘤是中枢神经系统最常见的脑肿瘤。传统的治疗方法不能有效治愈这种疾病。实验证据表明，67 kDa弹性蛋白-层粘连蛋白受体（67 LR）亚基是一种高亲和力的非整联蛋白层粘连蛋白结合蛋白，其在多种人类癌症的肿瘤细胞表面过表达，并与恶性细胞的较高增殖率和转移趋势直接相关。方法：本研究通过免疫组化染色和Western blotting检测67 LR在高级别星形细胞瘤中的表达，并通过构建干扰RNA表达质粒，研究67 LR在胶质瘤细胞系U251中的表达。结果显示，相对于正常脑组织样品，67 LR在高级别星形细胞瘤中具有增强的过表达，并且在通过RNAi下调67 LR基因后，胶质瘤细胞的迁移活性降低。假设低水平的67 LR表达可以降低胶质瘤细胞的迁移活性，这进一步证明67 LR通过介导肿瘤细胞功能导致肉瘤形成而在胶质瘤侵袭中发挥重要作用。该研究为神经胶质瘤的基因治疗提供了一种新的替代方案。(C)2009 Elsevier Inc. All rights reserved.
Objectives: Glioma is the most common brain tumor in central nervous system. Traditional therapies are not effective to cure this disease. Experimental evidence indicates that the 67 kDa elastin-laminin receptor (67LR) subunit is a high-affinity non-integrin laminin-binding protein that is over-expressed on the tumor cell surface in a variety of human carcinomas, and directly correlates with a higher proliferation rate of malignant cells and tendency to metastasise. However, little is known of the expression and function of 67LR in glioma cells.Methods: In this study, we estimated whether 67LR was constitutively over-expressed in high-grade astrocytomas by immunohistochemical staining and Western blotting, and investigated the role of a low level of 67LR expression in glioma cell line-U251 by constructing an interfering RNA expression plasmid.Results: The results showed that the 67LR had an enhanced over-expression in high-grade astrocytomas against normal brain tissues samples, and that the migratory activity of glioma cells was reduced after the down-regulation of the 67LR gene by RNAiDiscussion: It was hypothesized that a low level of 67LR expression could reduce migratory activity of glioma cells, which further proved that 67LR played an important role in glioma invasion by mediating tumor cell functions leading to sarcomata. This study provided a new alternative to gene therapy for glioma treatment. (C) 2009 Elsevier Inc. All rights reserved.