Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal
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Xu Sun1,*, Xiaotang Ma2,*, Jinju Wang3, Yuhui Zhao4, Yue Wang3, Ji C. Bihl3, Yanfang Chen2,3, Chuanlu Jiang1
1Department of Neurosurgery, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China
2Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
3Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA
4Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510000, China
*These authors equally contributed to this work
Xu Sun, email: firstname.lastname@example.org
Chuanlu Jiang, email: email@example.com
Keywords: GSCs, exosomes, miR-21, VEGF, angiogenesis
Received: January 16, 2017 Accepted: March 21, 2017 Published: March 29, 2017
Glioma stem cells (GSCs) play an important role in glioblastoma prognosis. Exosomes (EXs) mediate cell communication by delivering microRNAs (miRs). Glioblastoma has a high level of miR-21 which could upregulate vascular endothelial growth factor (VEGF) expression. We hypothesized GSC-EXs can promote the angiogenic ability of endothelial cells (ECs) through miR-21/VEGF signal. GSCs were isolated from U-251 cells with stem cell marker CD133. GSCs transfected without or with scramble or miR-21 mimics were used to produce GSC-EXscon, GSC-EXssc and GSC-EXsmiR-21. Human brain ECs were co-cultured with vehicle, GSC-EXscon, GSC-EXssc or GSC-EXsmiR-21 plus VEGF siRNAs (siRNAVEGF). After 24 hours, the angiogenic abilities of ECs were evaluated. The levels of miR-21, VEGF and p-Flk1/VEGFR2 were determined. Results showed: 1) Over 90% of purified GSCs expressed CD133; 2) The levels of miR-21 and VEGF in GSCs and GSC-EXs were up-regulated by miR-21 mimic transfection; 3) Compared to GSC-EXscon or GSC-EXssc, GSC-EXsmiR-21 were more effective in elevating the levels of miR-21 and VEGF, and the ratio of p-Flk1/VEGFR2 in ECs; 4) GSC-EXsmiR-21 were more effective in promoting the angiogenic ability of ECs than GSC-EXscon or GSC-EXssc, which were remarkably reduced by siRNAVEGF pretreatment. In conclusion, GSC-EXs can promote the angiogenic ability of ECs by stimulating miR-21/VEGF/VEGFR2 signal pathway.
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