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

Brain Tumor Pathology, ISSN: 1433-7398, Vol: 28, Issue: 2, Page: 89-97
2011
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Review Description

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 stemlike 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. © The Japan Society of Brain Tumor Pathology 2010.

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