...
首页> 外文期刊>Neuro-Oncology >Osteopontin increases heme oxygenase-1 expression and subsequently induces cell migration and invasion in glioma cells
【24h】

Osteopontin increases heme oxygenase-1 expression and subsequently induces cell migration and invasion in glioma cells

机译:骨桥蛋白增加血红素加氧酶-1表达,并随后诱导神经胶质瘤细胞迁移和侵袭

获取原文
获取原文并翻译 | 示例
           

摘要

Malignant gliomas are associated with high morbidity and mortality because they are highly invasive into surrounding brain tissue, making complete surgical resection impossible. Osteopontin is abundantly expressed in the brain and is involved in cell adhesion, migration, and invasion. The aim of the present study was to investigate the mechanisms of glioma cell migration. Migration and invasion activity were determined by transwell and wound-healing assays. Gene and protein expressions were analyzed by reverse transcription - PCR, real time-PCR, and Western blotting. Nrf2-DNA binding activity was determined by electrophoretic mobility shift assay. Establishment of migration-prone sublines were performed to select highly migratory glioma. An intracranial xenograft mouse model was used for the in vivo study. Application of recombinant human osteopontin enhanced the migration of glioma cells. Expression of heme oxygenase (HO)-l mRNA and protein also increased in response to osteopontin stimulation. Osteopontin-induced increase in cell migration was antagonized by HO-1 inhibitor or HO-1 small interfering (si)RNA. Osteopontin-mediated HO-1 expression was reduced by treatment with MEK/ERK and phosphatidylinositol 3-kinase/Akt inhibitors, as well as siRNA against Nrf2. Furthermore, osteopontin stimulated Nrf2 accumulation in the nucleus and increased Nrf2-DNA binding activity. In migration-prone sublines, cells with greater migration ability had higher osteopontin and HO-1 expression, and zinc protopor- phyrin IX treatment could effectively reduce the enhanced migration ability. In an intracranial xenograft mouse model, transplantation of migration-prone subline cells exhibited higher cell migration than parental tumor cells. These results indicate that osteopontin activates Nrf2 signaling, resulting in enhanced HO-1 expression and cell migration in glioma cells.
机译:恶性神经胶质瘤的发病率高,死亡率高,因为它们对周围的脑组织具有高度的侵袭性,不可能进行完全的手术切除。骨桥蛋白在脑中大量表达,并参与细胞粘附,迁移和侵袭。本研究的目的是研究神经胶质瘤细胞迁移的机制。迁移和侵袭活性通过transwell和伤口愈合测定法确定。通过逆转录-PCR,实时PCR和Western印迹分析基因和蛋白质的表达。 Nrf2-DNA结合活性是通过电泳迁移率变动分析确定的。建立易于迁移的亚系以选择高度迁徙的神经胶质瘤。颅内异种移植小鼠模型用于体内研究。重组人骨桥蛋白的应用增强了胶质瘤细胞的迁移。响应骨桥蛋白刺激,血红​​素加氧酶(HO)-1 mRNA和蛋白质的表达也增加。骨桥蛋白诱导的细胞迁移增加被HO-1抑制剂或HO-1小干扰(si)RNA拮抗。通过MEK / ERK和磷脂酰肌醇3-激酶/ Akt抑制剂以及针对Nrf2的siRNA处理,骨桥蛋白介导的HO-1表达降低。此外,骨桥蛋白刺激Nrf2在细胞核中积累并增加Nrf2-DNA结合活性。在易迁移亚系中,具有更高迁移能力的细胞具有更高的骨桥蛋白和HO-1表达,锌原卟啉IX处理可以有效地降低增强的迁移能力。在颅内异种移植小鼠模型中,易迁移亚系细胞的移植表现出比亲代肿瘤细胞更高的细胞迁移。这些结果表明骨桥蛋白激活Nrf2信号传导,导致胶质瘤细胞中HO-1表达增强和细胞迁移。

著录项

  • 来源
    《Neuro-Oncology》 |2012年第11期|1367-1378|共12页
  • 作者单位

    Graduate Institute of Neural and Cognitive Sciences, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan;

    Cancer Research Center, Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan;

    Department of Colorectal Surgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung, Taiwan, Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan;

    Department of Pharmacology, China Medical University, Taichung, Taiwan;

    Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan;

    Division of General Surgery, Department of Surgery, Cardinal Tien Hospital, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    glioma; HO-1; migration; Nrf2; osteopontin;

    机译:胶质瘤HO-1;移民;Nrf2;骨桥蛋白;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号