基础医学与临床 ›› 2016, Vol. 36 ›› Issue (5): 615-620.

• 研究论文 • 上一篇    下一篇

体外共培养人骨髓间充质干细胞与乳腺癌细胞可促进癌细胞的侵袭和迁移能力

许鹏超1,李静2,赵春华3   

  1. 1. 四川大学
    2. 中国医学科学院基础医学研究所
    3. 中国医学科学院基础医学研究所组织工程中心
  • 收稿日期:2016-01-19 修回日期:2016-03-16 出版日期:2016-05-05 发布日期:2016-04-26
  • 通讯作者: 赵春华 E-mail:chunhuaz@public.tpt.tj.cn
  • 基金资助:
    国家自然科学基金

Human mesenchymal stem cells promote breast cancer cells migration and invasion by co-culture in vitro

  • Received:2016-01-19 Revised:2016-03-16 Online:2016-05-05 Published:2016-04-26

摘要: 目的 探讨人骨髓间充质干细胞(hBM-MSCs)与乳腺癌细胞共培养对癌细胞转移能力的影响。 方法 ELISA检测BM-MSCs分泌细胞因子的水平。Transwell小室将BM-MSCs与乳腺癌细胞系MCF-7和MDB-MA-231分别共培养,比较共培养前后乳腺癌细胞的侵袭和迁移能力。Western blot检测p-STAT3和p-ERK等信号通路的激活情况。实时定量RT-PCR检测侵袭转移相关基因MMP2和MMP9的表达水平。结果 BM-MSCs分泌大量的细胞因子HGF、IL6、VEGF和TGF-β1。与BM-MSCs共培养后,乳腺癌细胞MCF-7(P<0. 01)和MDB-MA-231(迁移P<0. 05,侵袭P<0. 01)迁移和侵袭能力显著增加,p-STAT3和p-ERK信号通路激活(P<0. 01),侵袭转移相关靶基因MMP2和MMP9表达水平上调(P<0. 01)。 结论 BM-MSCs 与乳腺癌细胞共培养可以促进乳腺癌细胞的迁移和侵袭。

关键词: 人骨髓间充质干细胞, 信号转导与转录活化因子3, 乳腺癌转移, 基质金属蛋白酶

Abstract: Objective To study the effect of human bone marrow derived MSCs (hBM-MSCs) on the migration and invasion capacity of breast cancer cells in co-culture system. Methods Cytokines secreted by BM-MSCs were detected using ELISA assay. Tumor microenvironments were mimicked by co-culturing of BM-MSCs with breast cancer cell lines (MCF-7 and MDB-MA-231) separately. Capacity of migration and invasion were compared after co-culture using Transwell system.Activation of signal transducer and activator of transcription 3 (STAT3) was detected by Western blot. Experession of metastasis-associated gene matrix metalloproteinases (MMP2 and MMP9) were detected by realtime RT-PCR. Result HGF, IL6, VEGF and TGF β 1 were detected in the medium of BM-MSCs. Co-culturing with BM-MSCs can significantly enhance the migration and invasion capacity of breast cancer cells (the migration and invasion of MCF-7: P<0.01; the migration of MDA-231: P<0. 05; the invasion of MDA-231: P<0. 05).Signaling pathway of p-STAT3 and p-ERK were activated dramatically(P<0.01), and the expression of MMP2 and MMP9 were increased markedly(P<0.01). Conclusions BM-MSCs may promote the migration and invasion capacity of breast cancer cells by indirect co-culture of the two cell lines.

Key words: mesenchymal stem cell, signal transducer and activator of transcription 3 (STAT3), MMPs (Matrix metalloproteinases), breast cancer metastasis

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