{"id":2356,"date":"2019-09-01T00:00:25","date_gmt":"2019-09-01T00:00:25","guid":{"rendered":"http:\/\/bergleslab.com\/?p=2356"},"modified":"2020-01-30T23:46:41","modified_gmt":"2020-01-30T23:46:41","slug":"venkataramani-2019","status":"publish","type":"post","link":"http:\/\/bergleslab.com\/index.php\/2019\/09\/01\/venkataramani-2019\/","title":{"rendered":"Glutamatergic synaptic input to glioma cells drives brain tumour progression."},"content":{"rendered":"
Nature.<\/a> 2019 Sep;573(7775):532-538. doi: 10.1038\/s41586-019-1564-x. Epub 2019 Sep 18.<\/div>\n

Glutamatergic synaptic input to glioma cells drives brain tumour progression.<\/h4>\n
Venkataramani V<\/a>1,<\/sup>2,<\/sup>3<\/sup>, Tanev DI<\/a>4,<\/sup>5,<\/sup>6<\/sup>, Strahle C<\/a>4<\/sup>, Studier-Fischer A<\/a>5,<\/sup>6<\/sup>, Fankhauser L<\/a>5,<\/sup>6<\/sup>, Kessler T<\/a>5,<\/sup>6<\/sup>, K\u00f6rber C<\/a>4<\/sup>, Kardorff M<\/a>4<\/sup>, Ratliff M<\/a>6,<\/sup>7<\/sup>, Xie R<\/a>5,<\/sup>6<\/sup>, Horstmann H<\/a>4<\/sup>, Messer M<\/a>5,<\/sup>6<\/sup>, Paik SP<\/a>4<\/sup>, Knabbe J<\/a>4<\/sup>, Sahm F<\/a>8,<\/sup>9<\/sup>, Kurz FT<\/a>10<\/sup>, Acikg\u00f6z AA<\/a>11<\/sup>, Herrmannsd\u00f6rfer F<\/a>4<\/sup>, Agarwal A<\/a>12,<\/sup>13<\/sup>, Bergles DE<\/a>13<\/sup>, Chalmers A<\/a>14<\/sup>, Miletic H<\/a>15,<\/sup>16<\/sup>, Turcan S<\/a>5<\/sup>, Mawrin C<\/a>17<\/sup>, H\u00e4nggi D<\/a>7<\/sup>, Liu HK<\/a>11<\/sup>, Wick W<\/a>5,<\/sup>6<\/sup>, Winkler F<\/a>18,<\/sup>19<\/sup>, Kuner T<\/a>20<\/sup>.<\/div>\n
<\/div>\n

<\/h4>\n

ABSTRACT<\/h4>\n

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.
\n<\/br>
\n1 Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany. varun.venkataramani@med.uni-heidelberg.de.
\n2 Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. varun.venkataramani@med.uni-heidelberg.de.
\n3 Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. varun.venkataramani@med.uni-heidelberg.de.
\n4 Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
\n5 Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
\n6 Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
\n7 Neurosurgery Clinic, University Hospital Mannheim, Mannheim, Germany.
\n8 Department of Neuropathology, Institute of Pathology, Ruprecht-Karls University Heidelberg, Heidelberg, Germany.
\n9 Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
\n10 Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany.
\n11 Division of Molecular Neurogenetics, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
\n12 The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
\n13 CHS Research Group, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
\n14 Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
\n15 Department of Biomedicine, University of Bergen, Bergen, Norway.
\n16 Department of Pathology, Haukeland University Hospital, Bergen, Norway.
\n17 Institute for Neuropathology, Otto-von-Guericke University, Magdeburg, Germany.
\n18 Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. frank.winkler@med.uni-heidelberg.de.
\n19 Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. frank.winkler@med.uni-heidelberg.de.
\n20 Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany. thomas.kuner@uni-heidelberg.de.<\/p>\n

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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.<\/p>\n","protected":false},"author":1,"featured_media":2357,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78,33],"tags":[91,145,64,146],"class_list":["post-2356","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-original-research","category-publications","tag-ampa-receptor","tag-glioma","tag-glutamate","tag-glutamate-receptor"],"_links":{"self":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2356","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/comments?post=2356"}],"version-history":[{"count":4,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2356\/revisions"}],"predecessor-version":[{"id":2362,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2356\/revisions\/2362"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media\/2357"}],"wp:attachment":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media?parent=2356"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/categories?post=2356"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/tags?post=2356"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}