IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5196.html
   My bibliography  Save this article

Disruption of astrocyte–vascular coupling and the blood–brain barrier by invading glioma cells

Author

Listed:
  • Stacey Watkins

    (Center for Glial Biology in Medicine, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC 425)

  • Stefanie Robel

    (Center for Glial Biology in Medicine, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC 425)

  • Ian F. Kimbrough

    (Center for Glial Biology in Medicine, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC 425)

  • Stephanie M. Robert

    (Center for Glial Biology in Medicine, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC 425)

  • Graham Ellis-Davies

    (Mount Sinai School of Medicine, 1468 Madison Avenue, Annenberg Building Floor Ann22)

  • Harald Sontheimer

    (Center for Glial Biology in Medicine, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC 425)

Abstract

Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood–brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumours that use the perivascular space for invasion and co-opt existing vessels as satellite tumour form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of preexisting vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over the regulation of vascular tone through Ca2+-dependent release of K+. These findings have important clinical implications regarding blood flow in the tumour-associated brain and the ability to locally deliver chemotherapeutic drugs in disease.

Suggested Citation

  • Stacey Watkins & Stefanie Robel & Ian F. Kimbrough & Stephanie M. Robert & Graham Ellis-Davies & Harald Sontheimer, 2014. "Disruption of astrocyte–vascular coupling and the blood–brain barrier by invading glioma cells," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5196
    DOI: 10.1038/ncomms5196
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5196
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5196?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
    ---><---

    Citations

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


    Cited by:

    1. William A. Mills & AnnaLin M. Woo & Shan Jiang & Joelle Martin & Dayana Surendran & Matthew Bergstresser & Ian F. Kimbrough & Ukpong B. Eyo & Michael V. Sofroniew & Harald Sontheimer, 2022. "Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age," Nature Communications, Nature, vol. 13(1), pages 1-15, 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:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5196. 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.