TY - JOUR
T1 - Glutamatergic synaptic input to glioma cells drives brain tumour progression
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
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/9/26
Y1 - 2019/9/26
N2 - 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.
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.
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U2 - 10.1038/s41586-019-1564-x
DO - 10.1038/s41586-019-1564-x
M3 - Article
C2 - 31534219
AN - SCOPUS:85072687457
SN - 0028-0836
VL - 573
SP - 532
EP - 538
JO - Nature
JF - Nature
IS - 7775
ER -