中国医科大学学报

中国医科大学学报

中国医科大学学报 ›› 2013, Vol. 42 ›› Issue (11): 965–969.

• 论著 • 上一篇    下一篇

骨髓间充质干细胞向人胶质瘤迁移的分子机制初探

胡宜1,程鹏2,薛一雪3,刘云会1   

  1. 中国医科大学1.附属盛京医院神经外科,沈阳110004;
    2.附属第一医院神经外科,沈阳110004;
    3.基础医学院神经生物教研室,沈阳110004
  • 收稿日期:2013-07-25 出版日期:2013-11-30 发布日期:2013-11-28
  • 基金资助:
    国家自然科学基金(30901781)

Molecular Mechanism of the Tropism of Bone Marrow-derived Mesenchymal Stem Cells toward Glioma

HU Yi1,CHENG Peng2,XUE Yi-xue3,LIU Yun-hui1   

  1. 1. Department of Neurosurgery,Shengjing Hospital,China Medical University,Shenyang 110004,China;
    2. Department of Neurosurgery,The First Hospital,China Medical University,Shenyang 110004,China;
    3. Department of Neurobiology,College of Basic Medicine,China Medical University,Shenyang 110004,China
  • Received:2013-07-25 Online:2013-11-30 Published:2013-11-28

摘要: 目的研究细胞表面粘附分子在骨髓间充质干细胞(BMSCs)向胶质瘤定向迁移中的作用及其下游信号通路,探讨此过程中的分子生物学机制。方法骨髓间充质干细胞分离自6周龄的SD大鼠,采用全骨髓贴壁法原代培养。利用Transwell小室构建骨髓间充质干细胞体外迁移模型,观察人U251胶质瘤细胞诱导BMSCs趋化迁移的过程中,血管细胞粘附分子-1(VCAM-1)阻滞抗体及磷脂酰肌醇-3-激酶(PI3K)信号通路抑制剂LY294002对BMSCs迁移能力的影响。利用U251细胞培养上清诱导BMSCs,加入或不加入LY294002,利用RT-PCR及Westernblot方法观察VCAM-1的核酸及蛋白表达变化情况。结果加入VCAM-1阻滞抗体及LY294002后,BMSCs向U251胶质瘤细胞的迁移受到显著抑制;U251细胞能促进BMSCs的VCAM-1核酸及蛋白表达,加入LY294002后上调的VCAM-1表达受到抑制。结论胶质瘤细胞可通过促进BMSCs上调表达VCAM-1而促进其迁移,在此过程中PI3K信号通路发挥作用。

关键词: 骨髓间充质干细胞, 胶质瘤, 迁移, 粘附分子, 信号通路

Abstract: Objectives To investigate the role of cell surface adhesion molecule in the migration of bone marrow-derived mesenchymal stem cells (BMSCs) toward glioma and explore the relating molecular mechanism. Methods BMSCs were isolated from 4-6 week old Sprague-Dawley rats and purified by the attachment to culture plates. The influence of blocking antibody against vascular cell adhesion molecule-1 (VCAM-1) and inhibitor of phosphoinositide-3-kinase (PI3K) pathway (LY294002) on the migratory ability of BMSCs to human U251 glioma cells was checked using Transwell in vitro migration assay. BMSCs were treated with the conditioned medium of U251 glioma cells (with or without LY294002),and the expression levels of VCAM-1 mRNA and protein were determined by RT-PCR and Western blot assays. Results The migration of BMSCs toward glioma was significantly impaired by the treatment of blocking antibody against VCAM-1 and LY294002. Conditioned medium of U251 glioma cells significantly promoted the expressions of VCAM-1 mRNA and protein on BMSCs. The up-regulated expression VCAM-1 was inhibited by the treatment of LY294002. Conclusion Glioma cells induce the migration of BMSCs by promoting the expression of VCAM-1,and PI3K signal pathway was also involved in the process.

Key words: bone marrow-derived mesenchymal stem cells, glioma, migration, adhesion molecule, signal pathway

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