Glutamatergic synaptic input to glioma cells drives brain tumour progression

Varun Venkataramani (), Dimitar Ivanov Tanev, Christopher Strahle, Alexander Studier-Fischer, Laura Fankhauser, Tobias Kessler, Christoph Körber, Markus Kardorff, Miriam Ratliff, Ruifan Xie, Heinz Horstmann, Mirko Messer, Sang Peter Paik, Johannes Knabbe, Felix Sahm, Felix T. Kurz, Azer Aylin Acikgöz, Frank Herrmannsdörfer, Amit Agarwal, Dwight E. Bergles, Anthony Chalmers, Hrvoje Miletic, Sevin Turcan, Christian Mawrin, Daniel Hänggi, Hai-Kun Liu, Wolfgang Wick, Frank Winkler () and Thomas Kuner ()
Additional contact information
Varun Venkataramani: Heidelberg University
Dimitar Ivanov Tanev: Heidelberg University
Christopher Strahle: Heidelberg University
Alexander Studier-Fischer: University Hospital Heidelberg
Laura Fankhauser: University Hospital Heidelberg
Tobias Kessler: University Hospital Heidelberg
Christoph Körber: Heidelberg University
Markus Kardorff: Heidelberg University
Miriam Ratliff: Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
Ruifan Xie: University Hospital Heidelberg
Heinz Horstmann: Heidelberg University
Mirko Messer: University Hospital Heidelberg
Sang Peter Paik: Heidelberg University
Johannes Knabbe: Heidelberg University
Felix Sahm: Ruprecht-Karls University Heidelberg
Felix T. Kurz: University Hospital Heidelberg
Azer Aylin Acikgöz: Division of Molecular Neurogenetics, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ)
Frank Herrmannsdörfer: Heidelberg University
Amit Agarwal: Johns Hopkins University School of Medicine
Dwight E. Bergles: Heidelberg University
Anthony Chalmers: University of Glasgow
Hrvoje Miletic: University of Bergen
Sevin Turcan: University Hospital Heidelberg
Christian Mawrin: Otto-von-Guericke University
Daniel Hänggi: University Hospital Mannheim
Hai-Kun Liu: Division of Molecular Neurogenetics, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ)
Wolfgang Wick: University Hospital Heidelberg
Frank Winkler: University Hospital Heidelberg
Thomas Kuner: Heidelberg University

Nature, 2019, vol. 573, issue 7775, 532-538

Abstract: Abstract 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (9)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1564-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:573:y:2019:i:7775:d:10.1038_s41586-019-1564-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1564-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().