Format

Send to

Choose Destination
See comment in PubMed Commons below
J Neurosci. 2011 Mar 30;31(13):4858-67. doi: 10.1523/JNEUROSCI.3825-10.2011.

Bradykinin promotes the chemotactic invasion of primary brain tumors.

Author information

1
Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294.

Abstract

Primary brain tumors, gliomas, diffusely invade the brain by active cell migration either intraparenchymal, along white matter tracts or along blood vessels. The close relationship of glioma with the vasculature assures a continuous supply of oxygen and nutrients essential for cell growth, and exposes cells to a variety growth factors, chemokines, cytokines, and kinins. Signals that attract glioma cells to blood vessels are poorly understood. It has been shown that vascular endothelial cells can initiate the bradykinin (BK) signaling cascade and two bradykinin receptors, B1 and B2, have been identified and cloned. In this study we show that glioma cells isolated from patient biopsies express bradykinin 2 receptors (B2R) whose activation causes intracellular Ca(2+) oscillations. Through time-lapse video-microscopy experiments we show that BK significantly enhances glioma cell migration/invasion. We further show that BK acts as a chemoattractant guiding glioma cells toward blood vessels in acute rat brain slices. The number of cells associated with blood vessels is decreased when B2R are either pharmacologically inhibited or B2R eliminated through short-hairpin RNA knockdown. These data strongly suggest that bradykinin, acting via B2R, acts as an important signal directing the invasion of glioma cells toward blood vessels. A clinically approved B2R antagonist is available that could be used as anti-invasive drug in glioma patients in the future.

PMID:
21451024
PMCID:
PMC3096850
DOI:
10.1523/JNEUROSCI.3825-10.2011
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center