Exosomes derived from hypoxia-exposed glioma cells promotes glioma stem cell migration by JAK/STAT3 signalling pathway

Yue CHENG; Xiufeng YE

doi:10.16016/j.1000-5404.201909213

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Exosomes derived from hypoxia-exposed glioma cells promotes glioma stem cell migration by JAK/STAT3 signalling pathway

Basic Medicine | 更新时间：2026-01-09

- Exosomes derived from hypoxia-exposed glioma cells promotes glioma stem cell migration by JAK/STAT3 signalling pathway
- Journal of Third Military Medical University Vol. 42, Issue 4, Pages: 392-400(2020)
- 作者机构：
  
  400016 重庆，重庆医科大学基础医学院病理学教研室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201909213
  CLC： R364.4; R73-37; R730.264
- Received：28 September 2019，
  
  Revised：2019-12-05，
  
  Published：28 February 2020
- 稿件说明：
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Yue CHENG, Xiufeng YE. Exosomes derived from hypoxia-exposed glioma cells promotes glioma stem cell migration by JAK/STAT3 signalling pathway[J]. Journal of Third Military Medical University, 2020, 42(4): 392-400.
DOI：

Yue CHENG, Xiufeng YE. Exosomes derived from hypoxia-exposed glioma cells promotes glioma stem cell migration by JAK/STAT3 signalling pathway[J]. Journal of Third Military Medical University, 2020, 42(4): 392-400. DOI： 10.16016/j.1000-5404.201909213.

摘要

目的

探讨胶质瘤细胞在缺氧条件下分泌的外泌体对胶质瘤干细胞迁移的作用。

方法

超高速离心法提取缺氧和常氧条件下胶质瘤细胞分泌的外泌体，采用透射电子显微镜(TEM)和动态光散射(DLS)、Western blot检测等方法对外泌体进行鉴定；用DIO染料标记外泌体，荧光显微镜观察胶质瘤干细胞能否摄取外泌体。将PBS(空白组)、常氧(20%O

，常氧

组)和缺氧(1%O

，缺氧组)条件下提取的外泌体与胶质瘤干细胞共培养，CCK-8法测定胶质瘤干细胞增殖情况，Transwell实验检测胶质瘤干细胞迁移能力变化，Western blot检测JAK/STAT3通路蛋白磷酸化水平的改变。

结果

在胶质瘤干细胞的胞质中检测到外泌体携带的荧光染料DIO。CCK-8结果显示:提取的外泌体以不同浓度(浓度梯度依次为1、5、10、20、40 μg/mL)处理不同时间(12、24、48、72 h)后，常氧组和缺氧组胶质瘤干细胞的细胞活力差异无统计学意义。与空白组和常氧组比较，缺氧组提取外泌体共培养组的胶质瘤干细胞迁移能力显著提高(

0.05)，JAK/STAT3通路蛋白磷酸化水平也显著增加(

0.05)。

结论

胶质瘤细胞在缺氧条件下分泌的外泌体部分通过提高JAK/STAT3通路磷酸化水平促进胶质瘤干细胞迁移。

Abstract

Objective

To investigate the effect of exosomes secreted by hypoxia-exposed glioma cells on the migration ability of glioma stem cells

in vitro

Methods

Exosomes were isolated from glioma cells with hypoxia exposure or in normoxic culture by ultracentrifugation and identified by transmission electron microscopy

dynamic light scattering and Western blotting. The exosomes were labeled with DIO to allow observation of their intake by glioma stem cells under fluorescent microscope. The glioma stem cells were co-cultured with the exosomes or PBS for 24

or 72 h

and CCK-8 assay and Transwell assay were performed to assess the changes in the proliferation and migration ability of the cells. The changes in the phosphorylation levels of the proteins in the JAK/STAT3 pathway were detected using Western blotting.

Results

Fluorescence signals were detected in the glioma stem cells co-cultured with the DIO-labeled exosomes. The results of CCK-8 assay showed that the glioma stem cells showed no significant changes in their proliferative activity after co-culture with the exosomes from the glioma cells with or without hypoxic treatment. Co-culture with the exosomes from hypoxia-exposed glioma cells enhanced the migration ability of glioma stem cells

as compared with treatment with PBS or exosomes derived from normally cultured glioma cells (

0.05). The exosomes from hypoxia-exposed glioma cells also significantly increased the phosphorylation levels of the proteins in the JAK/STAT3 pathway.

Conclusion

Co-culture with exosomes from hypoxia-exposed glioma cells can enhance the migration ability of glioma stem cells partly by increasing the phosphorylation levels of the JAK/STAT3 pathway proteins.

关键词

Keywords

references

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