L. Patrussi and C. T. Baldari Pages 497 - 512 ( 16 )
The seven-spanning transmembrane G-protein coupled receptor CXCR4, which specifically binds to the chemokine CXCL12, is expressed on many cell types, including various types of tumour cells. CXCR4 plays a crucial role in organ-specific metastasis, directing migration of malignant cells expressing this receptor toward microenvironments where the cognate ligand is secreted. CXCL12 has a direct growth and survival-promoting effect for various cancer cells and enhances moreover tumour angiogenesis by recruiting endothelial progenitor cells to tumours. Drugs which modulate the CXCL12/CXCR4 axis are therefore promising candidates in anti-cancer therapies. CXCR4 is also a coreceptor for human immunodeficiency virus type 1 (HIV-1) X4 virus and, as such, plays an important role in virus entry into target cells. Hence, antiviral agents that bind to CXCR4 are expected to inhibit HIV-1 entry. Here we review the structure, mechanism of action and biological activity of the main CXCR4 antagonists (peptide inhibitors, non-peptide antagonists, neutralizing antibodies, modified analogues of CXCL12) and agonists (CXCL12 peptide analogues) and discuss the CXCL12/CXCR4 axis as an important target in development of anti-tumoral and anti-HIV-1 therapies.
CXCR4,CXCL12,antagonist,agonist,analogue,cancer,HIV-1,hematopoietic progenitor mobilization,cognate ligand,angiogenesis,human immunodeficiency virus type 1,peptide inhibitors,,chemokine receptors,G-protein coupled receptor (GPCR),bone marrow,lymph nodes,lung,brain,liver,peptide,Tachypleus tridentatus,Limulus polyphemus,TZ14004,TN14003,TC14012,4F-benzoyl-TN14003,T-140-Based Cyclic Pentapeptides,Linear T140-Based Oligopeptides,tripeptide mimetics,p-fluorobenzoylated tripeptide mimetics,AMD3100,AMD3100-Based Non-Cyclam Compounds,Dipicolylamine zinc(II)-Based Compounds,HSEFFR-CPC-RFFESH,aberrant hematopoiesi,homodimerization,Epstein-Barr virus-encoded
, Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.