Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587

被引:203
作者
Figueroa, Javier [1 ]
Phillips, Lynette M. [1 ]
Shahar, Tal [1 ]
Hossain, Anwar [1 ]
Gumin, Joy [1 ]
Kim, Hoon [2 ]
Bean, Andrew J. [3 ]
Calin, George A. [4 ]
Fueyo, Juan [5 ]
Walters, Edgar T. [6 ]
Kalluri, Raghu [7 ]
Verhaak, Roel G. [2 ]
Lang, Frederick F. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA
[3] Univ Texas Hlth Sci Ctr Houston, Dept Neurobiol & Anat, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA
[6] Univ Texas Hlth Sci Ctr Houston, Dept Integrated Biol & Pharmacol, Houston, TX 77030 USA
[7] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
关键词
EXTRACELLULAR VESICLES; GENE-EXPRESSION; CO-REPRESSORS; STROMAL CELLS; BRAIN-TUMOR; CANCER; GLIOBLASTOMA; MICRORNA; MICROENVIRONMENT; BIOMARKERS;
D O I
10.1158/0008-5472.CAN-16-2524
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC-derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. (C) 2017 AACR.
引用
收藏
页码:5808 / 5819
页数:12
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