Glutamatergic synaptic input to glioma cells drives brain tumour progression

Venkataramani, Varun and Tanev, Dimitar Ivanov and Strahle, Christopher and Studier-Fischer, Alexander and Fankhauser, Laura and Kessler, Tobias and Körber, Christoph and Kardorff, Markus and Ratliff, Miriam and Xie, Ruifan and Horstmann, Heinz and Messer, Mirko and Paik, Sang Peter and Knabbe, Johannes and Sahm, Felix and Kurz, Felix T. and Acikgöz, Azer Aylin and Herrmannsdörfer, Frank and Agarwal, Amit and Bergles, Dwight E. and Chalmers, Anthony and Miletic, Hrvoje and Turcan, Sevin and Mawrin, Christian and Hänggi, Daniel and Liu, Hai-Kun and Wick, Wolfgang and Winkler, Frank and Kuner, Thomas. (2019) Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature, 573 (7775). pp. 532-538.

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Official URL: https://edoc.unibas.ch/75631/

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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.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Kardorff, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Mar 2020 08:43
Deposited On:21 Feb 2020 08:17

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