miR-210参与调控间充质干细胞向肿瘤相关成纤维细胞转化

基础医学与临床 ›› 2018, Vol. 38 ›› Issue (6): 780-786.

miR-210参与调控间充质干细胞向肿瘤相关成纤维细胞转化

陈桦,李静,赵春华

中国医学科学院基础医学研究所

收稿日期:2018-03-14 修回日期:2018-04-20 出版日期:2018-06-05 发布日期:2018-05-25
通讯作者: 赵春华 E-mail:18310100813@163.com
基金资助:
中国医学科学院医学与健康科技创新工程经费资助

miR-210 plays a role in the transformation from mesenchymal stem cells (MSCs) into cancer-associated fibroblasts (CAFs)

Received:2018-03-14 Revised:2018-04-20 Online:2018-06-05 Published:2018-05-25

摘要/Abstract

摘要： 目的探讨miR-210是否在乳腺癌细胞诱导人脂肪来源间充质干细胞（hAD-MSCs）向肿瘤相关成纤维细胞（CAFs）转化中发挥作用。方法 Transwell 小室将乳腺癌细胞系MCF-7和MDA-MB-231分别与hAD-MSCs共培养， RT-qPCR检测不同时间点（0、3、6及9 d）收取乳腺癌细胞中miR-210的表达； RT-qPCR检测共培养后hAD-MSCs向CAFs转化及CAFs相关特征标志物平滑肌肌动蛋白- α（α-SMA）和腱生蛋白- c（tenascin-c）的基因表达，用Western blot检测α-SMA和成纤维细胞活化蛋白-α（FAPA）的蛋白表达；慢病毒分别向乳腺癌细胞转导miR-210抑制剂和miR-NC，然后与同比例的MSCs混合注射到裸鼠皮下，动态观察肿瘤的生长情况，4周后分离提取肿瘤组织中的CAFs，RT-qPCR和Western blot检测CAFs中α-SMA、FAPA 和波形蛋白（vimentin）的表达。结果与hAD-MSCs共培养后，乳腺癌细胞MCF-7和MDA-MB-231细胞中miR-210表达都持续上调（P<0. 05）。共培养条件下抑制肿瘤细胞表达miR-210可以抑制MSCs向CAFs转化（P<0. 05）。抑制肿瘤细胞miR-210的表达可以降低肿瘤生长（P<0. 05）。结论 miR-210作为一种重要的信息分子，介导了肿瘤微环境中MSCs向CAFs转化。

关键词: miR-210, 间充质干细胞, 肿瘤相关成纤维细胞, 乳腺癌细胞

Abstract: Objective To investigate whether miR-210 played a crucial role in the process of inducing the transformation from co-cultured adipose derived(AD)-MSCs into CAFs. Methods Co-cultured adipose derived (AD)-MSCs with breast cancer cells (BCCs) lines in vitro and detected the expression of miR-210 using RT-qPCR. The expression of CAFs characteristic markers including α-SMA and tenascin-c were measured by RT-qPCR and the expression of α-SMA and FAPA were assessed by Western blot. Co-injected MCF-7 cells transfected with miR-210 inhibitor or miR-NC with MSC at 1: 1 ratio into the immunodeficient nude mice subcutaneously and observed tumor growth in vivo constantly. Results miR-210 were all up-regulated when a variety of breast cancer cells were co-cultured with MSCs (P<0.05). Inhibition of miR-210 in tumor cell could inhibit the transformation from MSCs into CAFs (P<0.05). Animal experiments further confirmed that inhibition of miR-210 in tumor cell could reduce tumor growth (P<0.05). Conclusion As an important information molecule, miR-210 mediates the transformation from MSCs to CAFs in the tumor microenvironment.

Key words: miR-210, mesenchymal stem cells , cancer-associated fibroblasts , breast cancer cells

陈桦李静赵春华. miR-210参与调控间充质干细胞向肿瘤相关成纤维细胞转化[J]. 基础医学与临床, 2018, 38(6): 780-786.

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