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CXCL12/CXCR4 signaling in malignant brain tumors: a potential pharmacological therapeutic target

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Abstract

Chemokines are 8- to 12-kDa peptides that function as chemoattractant cytokines involved in cell activation, differentiation, and trafficking. Chemokines bind to specific G-protein-coupled, seven-span transmembrane receptors on the plasma membrane of target cells. Chemokine (C-X-C motif) ligand 12 (CXCL12), an alpha-chemokine that binds to G-protein-coupled chemokine (C-X-C motif) receptor 4 (CXCR4), plays an important and unique role in the regulation of stem/progenitor-cell trafficking. As CXCR4 is expressed on several cancer cells, these CXCR4-positive cancer cells may metastasize to organs that secrete/express CXCL12. Regarding brain tumors, recent data demonstrate that glioma tumor stem-like cells promote tumor angiogenesis and vasculogenesis via the CXCL12/CXCR4 pathway. In addition, CXCL12/CXCR4 have recently been shown to be expressed in primary central nervous system (PCNS) lymphomas, and a role for chemokines in the pathogenesis of PCNS lymphomas was suggested. This review focuses on current knowledge regarding the biology of the CXCL12/CXCR4 pathway in the context of understanding their potential role in malignant gliomas and PCNS lymphoma development. The CXCL12/CXCR4 interaction as a therapeutic target for malignant brain tumors is also discussed.

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Acknowledgments

This study was partly supported by a grant from the Ishibashi Foundation for the Promotion of Science.

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Authors and Affiliations

  1. Department of Neurosurgery, Kurume University School of Medicine, Kurume, Japan

    Mizuhiko Terasaki & Minoru Shigemori

  2. Department of Pathology, Kurume University School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan

    Yasuo Sugita, Fumiko Arakawa, Yosuke Okada & Koichi Ohshima

Authors
  1. Mizuhiko Terasaki
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  2. Yasuo Sugita
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  3. Fumiko Arakawa
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  4. Yosuke Okada
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  5. Koichi Ohshima
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  6. Minoru Shigemori
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Corresponding author

Correspondence to Yasuo Sugita.

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Terasaki, M., Sugita, Y., Arakawa, F. et al. CXCL12/CXCR4 signaling in malignant brain tumors: a potential pharmacological therapeutic target. Brain Tumor Pathol 28, 89–97 (2011). https://doi.org/10.1007/s10014-010-0013-1

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  • DOI: https://doi.org/10.1007/s10014-010-0013-1

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