骨肉瘤细胞外泌体调控JAK2/STAT3信号通路影响成纤维细胞向肿瘤相关成纤维细胞转化
DOI:
作者:
作者单位:

作者简介:

通讯作者:

基金项目:

国家自然科学基金地区科学基金项目(81860394/ H0607)


Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
    摘要:

    目的 探讨骨肉瘤外泌体对肿瘤相关成纤维细胞转化的影响及机制。方法 提取并鉴定骨肉瘤细胞U2-OS、MG-63,人成骨细胞hFoB1.19外泌体,将PBS、hFoB1.19、U2-OS、MG-63外泌体与人肺成纤维细胞MRC-5共孵育,CCK8法检测MRC-5增殖能力,Transwell小室法检测MRC5迁移和侵袭能力,qRT-PCR检测MRC-5细胞中炎症因子IL-1β、IL-6、IL-8表达,Western blot 检测MRC-5细胞α-SMA、Vimentin、FAP表达,JAK2/STAT3信号通路的激活。结果 透射电镜和Western blot鉴定所提取的外泌体符合其结构特征;与U2-OS、MG-63外泌体共孵育后,MRC-5增殖、迁移和侵袭能力显著增加,MRC-5中IL-1β、IL-6、IL-8表达显著增加,α-SMA、Vimentin、FAP表达显著增加,JAK2和STAT3磷酸化水平显著增加(均P<0.001)。结论 骨肉瘤细胞外泌体通过激活JAK2/STAT3信号通路而促进成纤维细胞向肿瘤相关成纤维细胞转化。

    Abstract:

    Objective To investigate the effect and mechanism of osteosarcoma exosomes on tumorassociated fibroblast transformation.Methods The exosomes of osteosarcoma cells U2-OS, Mg-63 and human osteoblasts hfob1-19 were extracted and identified. The exosomes of PBS, hFoB1-19, U2-OS and Mg-63 were incubated with human lung fibroblasts MRC-5. The proliferation ability of MRC-5 was detected by CCK8 method, the migration and invasion ability of MRC-5 was detected by Transwell chamber method, and the inflammatory factor IL-1 in MRC-5 cells was detected by QRTPCR-β、The expression of IL-6 and IL-8 was detected by Western blot-α The expression of SMA, vimentin and FAP, and the activation of JAK2/STAT3 signaling pathway. Results he exosomes were identified by transmission electron microscope and Western blot. When CO incubated with U2-OS and Mg-63 exosomes, the proliferation, migration and invasion of MRC 5 increased significantly; IL-1β, IL-6 and IL-8 in MRC 5 increased significantly; the expressions of α-SMA, vimentin and FAP were significantly increased, and the phosphorylation levels of JAK2 and STAT3 were significantly increased (all =P<0.001). Conclusion Osteosarcoma cell exosomes promote the transformation of fibroblasts into tumor-associated fibroblasts by activating JAK2/STAT3 signaling pathway.

    参考文献
    相似文献
    引证文献
引用本文
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2021-08-24
您是第位访问者
版权所有:《西部医学》编辑部     蜀ICP备18038379号-4
地址:四川省成都市武侯区小天竺街75号财富国际18F-1号    邮政编码:610041
电话:028-85570072/85588403    E-mail:xbyxqk@163.com
技术支持:北京勤云科技发展有限公司