@article{70d35288d0534c7f9edc3bb345d0ff3d,
title = "Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles",
abstract = "Emerging evidence suggests that crosstalk between glioma cells and the brain microenvironment may influence brain tumor growth. To date, known reciprocal interactions among these cells have been limited to the release of paracrine factors. Combining a genetic strategy with longitudinal live imaging, we find that individual gliomas communicate with distinct sets of non-glioma cells, including glial cells, neurons, and vascular cells. Transfer of genetic material is achieved mainly through extracellular vesicles (EVs), although cell fusion also plays a minor role. We further demonstrate that EV-mediated communication leads to the increase of synaptic activity in neurons. Blocking EV release causes a reduction of glioma growth in vivo. Our findings indicate that EV-mediated interaction between glioma cells and non-glioma brain cells alters the tumor microenvironment and contributes to glioma development.",
keywords = "astrocyte, cell fusion, exosome, extracellular vesicle, glia, glioma, interaction, neuron, tumor microenvironment",
author = "Xiaofei Gao and Zhaohuan Zhang and Tomoyuki Mashimo and Bo Shen and James Nyagilo and Hao Wang and Yihui Wang and Zhida Liu and Aditi Mulgaonkar and Hu, {Xiao Ling} and Piccirillo, {Sara Grazia Maria} and Ugur Eskiocak and Dav{\'e}, {Digant P.} and Song Qin and Yongjie Yang and Xiankai Sun and Yang-Xin Fu and Hui Zong and Wenzhi Sun and Bachoo, {Robert M.} and Wuping Ge",
note = "Funding Information: We thank C. Liu, Z.-L. Wang, and Children{\textquoteright}s Research Institute (CRI) colleagues S.J. Morrison, J. Xu, R. Deberardinis, H. Zhu, and P. Mishira for advice on the project; J.-M. Jia for advice on live imaging; R. Jackson, A. Darehshouri, and K. Luby-Phelps from the University of Texas Southwestern Medical Center (UTSW) Electron Microscopy Core Facility for imaging extracellular vesicles with electron microscopy; Y.-X. Sun for advice on glioma cell culture; and B. Samuels, H. Zhao, N.N. Lu, J. Hu, and L.-J. Wu for critical discussion and reading of the manuscript. This work is supported by the National Institute of Neurological Disorders and Stroke ( NINDS ) R01 ( R01NS104009 ), Jonesville Foundation for Pediatric Cancer , University of Texas Southwestern High Impact/High Risk funds, NINDS K99/R00 ( R00NS073735 ), and CRI start-up funds to W.-p.G.; National Institues of Health ( NIH ) grant R01NS065195 and Simmons Cancer Center NIH support grant 5P30CA142543 for R.M.B.; National Cancer Institute ( NCI ) grant R01-CA136495 to H.Z.; NCI grant CA141975 ; the CPRIT ( RR150072 ) to Y.-X.F.; National Natural Science Foundation of China (no. 31871477 ) and National Key Basic Research Program of China (973 Program, no. 2014CB965001 ) to S.Q.; the Cary Council—Southwestern Medical Foundation Award to S.G.M.P.; the Hamon Center for Regenerative Science and Medicine Awards for X.G.; Ruth L. Kirschstein National Research Service Award ( NRSA ) Postdoctoral Fellowship (F32) from NHLBI ( 1F32HL139016-01 ) to B.S.; and an NINDS Pathway to Independence Award and the Dan Adams Thinking Outside the Box Award (from The Henrietta B. and Frederick H. Bugher Foundation ) to W.-p.G. Funding Information: We thank C. Liu, Z.-L. Wang, and Children's Research Institute (CRI) colleagues S.J. Morrison, J. Xu, R. Deberardinis, H. Zhu, and P. Mishira for advice on the project; J.-M. Jia for advice on live imaging; R. Jackson, A. Darehshouri, and K. Luby-Phelps from the University of Texas Southwestern Medical Center (UTSW) Electron Microscopy Core Facility for imaging extracellular vesicles with electron microscopy; Y.-X. Sun for advice on glioma cell culture; and B. Samuels, H. Zhao, N.N. Lu, J. Hu, and L.-J. Wu for critical discussion and reading of the manuscript. This work is supported by the National Institute of Neurological Disorders and Stroke (NINDS) R01 (R01NS104009), Jonesville Foundation for Pediatric Cancer, University of Texas Southwestern High Impact/High Risk funds, NINDS K99/R00 (R00NS073735), and CRI start-up funds to W.-p.G.; National Institues of Health (NIH) grant R01NS065195 and Simmons Cancer Center NIH support grant 5P30CA142543 for R.M.B.; National Cancer Institute (NCI) grant R01-CA136495 to H.Z.; NCI grant CA141975; the CPRIT (RR150072) to Y.-X.F.; National Natural Science Foundation of China (no. 31871477) and National Key Basic Research Program of China (973 Program, no. 2014CB965001) to S.Q.; the Cary Council?Southwestern Medical Foundation Award to S.G.M.P.; the Hamon Center for Regenerative Science and Medicine Awards for X.G.; Ruth L. Kirschstein National Research Service Award (NRSA) Postdoctoral Fellowship (F32) from NHLBI (1F32HL139016-01) to B.S.; and an NINDS Pathway to Independence Award and the Dan Adams Thinking Outside the Box Award (from The Henrietta B. and Frederick H. Bugher Foundation) to W.-p.G. W.-p.G. X.G. and Z.Z. conceived the project. W.-p.G. X.G. Z.Z. and R.W.B. designed the experiments. X.G. performed all in vivo imaging experiments. X.G. Z.Z. H.W. and W.-p.G. completed most of the animal experiments and data analysis. W.S. assisted in designing and developing longitudinal live imaging. S.G.M.P. H.W. and T.M. prepared most of the glioma cells. B.S. and U.E. performed fluorescence-activated cell sorting. J.N. performed microfluidic channel imaging. A.M. and Z.L. measured EV size. W.-p.G. R.W.B. S.Q. Y.-X.F. X.S. Y.Y. and H.Z. provided reagents, cells, and animals. W.-p.G. and X.G. completed electrophysiological recordings. W.-p.G. and X.G. wrote the manuscript. All authors reviewed and edited the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = feb,
day = "25",
doi = "10.1016/j.celrep.2020.01.089",
language = "English (US)",
volume = "30",
pages = "2489--2500.e5",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}