TY  - JOUR
AU  - Venkataramani, Varun
AU  - Tanev, Dimitar Ivanov
AU  - Strahle, Christopher
AU  - Studier-Fischer, Alexander
AU  - Fankhauser, Laura
AU  - Kessler, Tobias
AU  - Körber, Christoph
AU  - Kardorff, Markus
AU  - Ratliff, Miriam
AU  - Xie, Ruifan
AU  - Horstmann, Heinz
AU  - Messer, Mirko
AU  - Paik, Sang Peter
AU  - Knabbe, Johannes
AU  - Sahm, Felix
AU  - Kurz, Felix T
AU  - Acikgöz, Azer Aylin
AU  - Herrmannsdörfer, Frank
AU  - Agarwal, Amit
AU  - Bergles, Dwight E
AU  - Chalmers, Anthony
AU  - Miletic, Hrvoje
AU  - Turcan, Sevin
AU  - Mawrin, Christian
AU  - Hänggi, Daniel
AU  - Liu, Hai-Kun
AU  - Wick, Wolfgang
AU  - Winkler, Frank
AU  - Kuner, Thomas
TI  - Glutamatergic synaptic input to glioma cells drives brain tumour progression.
JO  - Nature 
VL  - 573
IS  - 7775
SN  - 1476-4687
CY  - London [u.a.]
PB  - Nature Publ. Group52462
M1  - DKFZ-2019-02273
SP  - 532-538
PY  - 2019
N1  - DKFZ-ZMBH Alliance
AB  - A network of communicating tumour cells that is connected by tumour microtubes mediates the progression of incurable gliomas. Moreover, neuronal activity can foster malignant behaviour of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here we report a direct communication channel between neurons and glioma cells in different disease models and human tumours: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumour microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype. Neuronal activity including epileptic conditions generates synchronised calcium transients in tumour-microtube-connected glioma networks. Glioma-cell-specific genetic perturbation of AMPA receptors reduces calcium-related invasiveness of tumour-microtube-positive tumour cells and glioma growth. Invasion and growth are also reduced by anaesthesia and the AMPA receptor antagonist perampanel, respectively. These findings reveal a biologically relevant direct synaptic communication between neurons and glioma cells with potential clinical implications.
LB  - PUB:(DE-HGF)16
C6  - pmid:31534219
DO  - DOI:10.1038/s41586-019-1564-x
UR  - https://inrepo02.dkfz.de/record/144849
ER  -