IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v573y2019i7775d10.1038_s41586-019-1564-x.html
   My bibliography  Save this article

Glutamatergic synaptic input to glioma cells drives brain tumour progression

Author

Listed:
  • Varun Venkataramani

    (Heidelberg University
    University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Dimitar Ivanov Tanev

    (Heidelberg University
    University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Christopher Strahle

    (Heidelberg University)

  • Alexander Studier-Fischer

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Laura Fankhauser

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Tobias Kessler

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Christoph Körber

    (Heidelberg University)

  • Markus Kardorff

    (Heidelberg University)

  • Miriam Ratliff

    (Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    University Hospital Mannheim)

  • Ruifan Xie

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Heinz Horstmann

    (Heidelberg University)

  • Mirko Messer

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Sang Peter Paik

    (Heidelberg University)

  • Johannes Knabbe

    (Heidelberg University)

  • Felix Sahm

    (Ruprecht-Karls University Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • 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
    Heidelberg University)

  • Dwight E. Bergles

    (Heidelberg University)

  • Anthony Chalmers

    (University of Glasgow)

  • Hrvoje Miletic

    (University of Bergen
    Haukeland University Hospital)

  • 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
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Frank Winkler

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Thomas Kuner

    (Heidelberg University)

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.

Suggested Citation

  • Varun Venkataramani & Dimitar Ivanov Tanev & Christopher Strahle & Alexander Studier-Fischer & Laura Fankhauser & Tobias Kessler & Christoph Körber & Markus Kardorff & Miriam Ratliff & Ruifan Xie & He, 2019. "Glutamatergic synaptic input to glioma cells drives brain tumour progression," Nature, Nature, vol. 573(7775), pages 532-538, September.
    • Handle: RePEc:nat:nature:v:573:y:2019:i:7775:d:10.1038_s41586-019-1564-x
    DOI: 10.1038/s41586-019-1564-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-019-1564-x
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-019-1564-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yanming Ren & Zongyao Huang & Lingling Zhou & Peng Xiao & Junwei Song & Ping He & Chuanxing Xie & Ran Zhou & Menghan Li & Xiangqun Dong & Qing Mao & Chao You & Jianguo Xu & Yanhui Liu & Zhigang Lan & , 2023. "Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Corina Anastasaki & Juan Mo & Ji-Kang Chen & Jit Chatterjee & Yuan Pan & Suzanne M. Scheaffer & Olivia Cobb & Michelle Monje & Lu Q. Le & David H. Gutmann, 2022. "Neuronal hyperexcitability drives central and peripheral nervous system tumor progression in models of neurofibromatosis-1," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. William H. Tomaszewski & Jessica Waibl-Polania & Molly Chakraborty & Jonathan Perera & Jeremy Ratiu & Alexandra Miggelbrink & Donald P. McDonnell & Mustafa Khasraw & David M. Ashley & Peter E. Fecci &, 2022. "Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Ling Hai & Dirk C. Hoffmann & Robin J. Wagener & Daniel D. Azorin & David Hausmann & Ruifan Xie & Magnus-Carsten Huppertz & Julien Hiblot & Philipp Sievers & Sophie Heuer & Jakob Ito & Gina Cebulla & , 2024. "A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1," Nature Communications, Nature, vol. 15(1), pages 1-29, December.
    5. Yuanning Zheng & Francisco Carrillo-Perez & Marija Pizurica & Dieter Henrik Heiland & Olivier Gevaert, 2023. "Spatial cellular architecture predicts prognosis in glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Chaitali Chakraborty & Itzel Nissen & Craig A. Vincent & Anna-Carin Hägglund & Andreas Hörnblad & Silvia Remeseiro, 2023. "Rewiring of the promoter-enhancer interactome and regulatory landscape in glioblastoma orchestrates gene expression underlying neurogliomal synaptic communication," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Romain Sigaud & Thomas K. Albert & Caroline Hess & Thomas Hielscher & Nadine Winkler & Daniela Kocher & Carolin Walter & Daniel Münter & Florian Selt & Diren Usta & Jonas Ecker & Angela Brentrup & Mar, 2023. "MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:573:y:2019:i:7775:d:10.1038_s41586-019-1564-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.