Glutamatergic synaptic input to glioma cells drives brain tumour progression

被引：750

作者：

Venkataramani, Varun ^{[1
,2
,3
]}

Tanev, Dimitar Ivanov ^{[1
,2
,3
]}

Strahle, Christopher ^{[1
]}

Studier-Fischer, Alexander ^{[2
,3
]}

Fankhauser, Laura ^{[2
,3
]}

Kessler, Tobias ^{[2
,3
]}

Koerber, Christoph ^{[1
]}

Kardorff, Markus ^{[1
]}

Ratliff, Miriam ^{[3
,4
]}

Xie, Ruifan ^{[2
,3
]}

Horstmann, Heinz ^{[1
]}

Messer, Mirko ^{[2
,3
]}

Paik, Sang Peter ^{[1
]}

Knabbe, Johannes ^{[1
]}

Sahm, Felix ^{[5
,6
,7
]}

Kurz, Felix T. ^{[7
]}

Acikgoez, Azer Aylin ^{[8
]}

Herrmannsdoerfer, Frank ^{[1
]}

Agarwal, Amit ^{[9
,10
]}

Bergles, Dwight E. ^{[10
]}

Chalmers, Anthony ^{[11
]}

Miletic, Hrvoje ^{[12
,13
]}

Turcan, Sevin ^{[2
]}

Mawrin, Christian ^{[14
]}

Haenggi, Daniel ^{[4
]}

Liu, Hai-Kun ^{[8
]}

Wick, Wolfgang ^{[2
,3
]}

Winkler, Frank ^{[2
,3
]}

Kuner, Thomas ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Funct Neuroanat, Inst Anat & Cell Biol, Heidelberg, Germany

[2] Univ Heidelberg Hosp, Neurol Clin & Natl Ctr Tumor Dis, Heidelberg, Germany

[3] German Canc Res Ctr, Clin Cooperat Unit Neurooncol, German Canc Consortium DKTK, Heidelberg, Germany

[4] Univ Hosp Mannheim, Neurosurg Clin, Mannheim, Germany

[5] Heidelberg Univ, Inst Pathol, Dept Neuropathol, Heidelberg, Germany

[6] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, German Canc Consortium DKTK, Heidelberg, Germany

[7] Univ Heidelberg Hosp, Dept Neuroradiol, Heidelberg, Germany

[8] German Canc Res Ctr, Div Mol Neurogenet, DKFZ ZMBH Alliance, Heidelberg, Germany

[9] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD USA

[10] Heidelberg Univ, Inst Anat & Cell Biol, Res Grp, Heidelberg, Germany

[11] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland

[12] Univ Bergen, Dept Biomed, Bergen, Norway

[13] Haukeland Hosp, Dept Pathol, Bergen, Norway

[14] Otto von Guericke Univ, Inst Neuropathol, Magdeburg, Germany

来源：

NATURE | 2019年 / 573卷 / 7775期

关键词：

RNA; GROWTH; DETERMINANT; MIGRATION; EPILEPSY; SEIZURES; RELEASE;

D O I：

10.1038/s41586-019-1564-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：532 / +

页数：24

共 37 条

[1] Clearance of glutamate inside the synapse and beyond [J].