title: CXCL12/CXCR4 signaling in malignant brain tumors: a potential pharmacological therapeutic target.
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.
authors.affiliation: Department of Neurosurgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Mizuhiko
authors.initials: M
authors.lastname: Terasaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugita
authors.forename: Fumiko
authors.initials: F
authors.lastname: Arakawa
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okada
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Minoru
authors.initials: M
authors.lastname: Shigemori
mesh_terms: D001596:Benzylamines; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080027:Cyclams; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor