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.
基金:
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]; CRI; National Institues of Health (NIH) [R01NS065195]; Simmons Cancer Center NIH support grant [5P30CA142543]; National Cancer Institute (NCI) [R01-CA136495]; NCI [CA141975]; CPRIT [RR150072]; National Natural Science Foundation of China [31871477]; National Key Basic Research Program of China (973 Program) [2014CB965001]; Cary Council-Southwestern Medical Foundation Award; Hamon Center for Regenerative Science and Medicine Awards; Ruth L. Kirschstein National Research Service Award (NRSA) Postdoctoral Fellowship (F32) from NHLBI [1F32HL139016-01]; NINDS; Dan Adams Thinking Outside the Box Award (The Henrietta B. and Frederick H. Bugher Foundation)