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The chemokine CXCL12 and its receptor CXCR4 promote glioma stem cell-mediated VEGF production and tumour angiogenesis via PI3K/AKT signalling

  1. Author:
    Ping, Y. F.
    Yao, X. H.
    Jiang, J. Y.
    Zhao, L. T.
    Yu, S. C.
    Jiang, T.
    Lin, M. C. M.
    Chen, J. H.
    Wang, B.
    Zhang, R.
    Cui, Y. H.
    Qian, C.
    Wang, J. M.
    Bian, X. W.

  2. Author Address

    [Ping, YF; Yao, XH; Jiang, JY; Zhao, LT; Yu, SC; Lin, MCM; Chen, JH; Wang, B; Zhang, R; Cui, YH; Qian, C; Bian, XW] Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China [Ping, YF; Yao, XH; Jiang, JY; Zhao, LT; Yu, SC; Lin, MCM; Chen, JH; Wang, B; Zhang, R; Cui, YH; Qian, C; Bian, XW] Third Mil Med Univ, SW Canc Ctr, Southwest Hosp, Chongqing 400038, Peoples R China [Jiang, T] Beijing Capital Med Univ, Dept Neurosurg, Tiantan Hosp, Beijing 100050, Peoples R China [Lin, MCM] Chinese Univ Hong Kong, Brain Tumour Ctr, Div Neurosurg, PWH, Shatin, Hong Kong, Peoples R China [Wang, JM] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA;Bian, XW (reprint author), Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China;bianxiuwu@263.net
    1. Year: 2011
    2. Date: Jul
  2. Journal: Journal of Pathology
    1. 224
    2. 3
    3. Pages: 344-354
  4. Type of Article: Article
  5. ISSN: 0022-3417
  1. Abstract:

    Chemokines and their receptors are actively involved in inflammation, immune responses, and cancer development. Here we report the detection of CD133(+) glioma stem-like cells (GSCs) co-expressing a chemokine receptor CXCR4 in human primary glioma tissues. These GSCs were located in areas adjacent to tumour vascular capillaries, suggesting an association between GSCs and tumour angiogenesis. To test this hypothesis, we isolated CD133(+) GSCs from surgical specimens of human primary gliomas and glioma cell lines. As compared to CD133(-) cells, CD133(+) GSCs expressed significantly higher levels of CXCR4 mRNA and protein, and migrated more efficiently in response to the CXCR4 ligand CXCL12. In addition, CXCL12 induced vascular endothelial growth factor (VEGF) production by CD133(+) GSCs via activation of the PI3K/AKT signalling pathway. Furthermore, knocking down of CXCR4 using RNA interference or inhibition of CXCR4 function by an antagonist AMD3100 not only reduced VEGF production by CD133(+) GSCs in vitro, but also attenuated the growth and angiogenesis of tumour xenografts in vivo formed by CD133(+) GSCs in SCID mice. These results indicate that CXCL12 and its receptor CXCR4 promote GSC-initiated glioma growth and angiogenesis by stimulating VEGF production. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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External Sources

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  2. DOI: 10.1002/path.2908
  3. View record in Web of Science®
  4. WOS: 000291389500008

Library Notes

  1. Fiscal Year: FY2010-2011
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