Transfer of MicroRNA via Macrophage-Derived Extracellular Vesicles Promotes Proneural-to-Mesenchymal Transition in Glioma Stem Cells

Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages triggered PMT in glioma stem cells (GSC) via s...

Full description

Saved in:
Bibliographic Details
Published in:Cancer immunology research 2020-07, Vol.8 (7), p.966-981
Main Authors: Zhang, Zongpu, Xu, Jianye, Chen, Zihang, Wang, Huizhi, Xue, Hao, Yang, Chunlei, Guo, Qindong, Qi, Yanhua, Guo, Xiaofan, Qian, Mingyu, Wang, Shaobo, Qiu, Wei, Gao, Xiao, Zhao, Rongrong, Guo, Xing, Li, Gang
Format: Article
Language:English
Subjects:
Animals
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Brain Neoplasms - radiotherapy
Cell Proliferation
Cells, Cultured
DNA Helicases - metabolism
DNA-Binding Proteins - metabolism
Extracellular Vesicles - genetics
Extracellular Vesicles - metabolism
Gene Expression Regulation, Neoplastic
Glioma - genetics
Glioma - metabolism
Glioma - pathology
Glioma - radiotherapy
Humans
Macrophages - metabolism
Mesenchymal Stem Cells - metabolism
Mesenchymal Stem Cells - pathology
Mice
Mice, Nude
MicroRNAs - genetics
MicroRNAs - metabolism
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Radiation Protection
Spheroids, Cellular
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages triggered PMT in glioma stem cells (GSC) via small extracellular vesicles (sEV). sEVs from monocyte-derived macrophages transferred , and to GSCs, and these miRNAs promoted several mesenchymal phenotypes in proneural (PN) GSCs by simultaneously targeting We found that CHD7 played a critical role in the maintenance of the PN phenotype, and knockdown significantly promoted PMT in GSCs via the RelB/P50 and p-STAT3 pathways. The induction of PMT by sEVs containing , and in a xenograft nude mouse model exacerbated radiotherapy resistance and thus decreased the benefits of radiotherapy. Collectively, these findings identified macrophage-derived sEVs as key regulators of PMT in GSCs and demonstrated that CHD7 is a novel inhibitor of PMT.
ISSN:2326-6066
2326-6074
DOI:10.1158/2326-6066.cir-19-0759