- Stromal cell-derived factor-1
stromal cell-derived factor-1) is small cytokinebelonging to the chemokinefamily that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12).
summary_text = For background information on chemokines, see CXCL11 (SCYB11; MIM 604852). Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the intercrine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF (see MIM 191160), or IL1 (see MIM 147760). The intercrines are characterized by the presence of 4 conserved cysteines which form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, which includes beta chemokine, the cysteine residues are adjacent to each other. In the CXC subfamily, which includes alpha chemokine, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group. [supplied by OMIM] [cite web | title = Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6387| accessdate = ]
SDF-1 is produced in two forms, SDF-1α/CXCL12a and SDF-1β/CXCL12b, by alternate splicing of the same gene. [De La Luz Sierra et al. Differential processing of stromal-derived factor-1alpha and beta explains functional diversity. Blood 103:2452-2459, 2004.] Chemokines are characterized by the presence of four conserved
cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid.
CXCL12 is strongly
chemotacticfor lymphocytes. [Bleul et al. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J. Exp. Med. 184: 1101-1109, 1996.] [Ara et al. Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1). Proc. Nat. Acad. Sci. 100: 5319-5323, 2003.] [Askari et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362: 697-703, 2003.] [Ma et al. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc. Nat. Acad. Sci. 95: 9448-9453, 1998.]
During embryogenesis it directs the migration of hematopoietic cells from foetal
liverto bone marrowand the formation of large blood vessels. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life.
In adulthood CXCL12 plays an important role in angiogenesis by recruiting endothelial progenitor cells (EPC) from the bone morrow through a CXCR4 dependent mechanism. [Zheng H, Fu G, Dai T, Huang H. Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway.J Cardiovasc Pharmacol. 2007 Sep;50(3):274-80.Click here to read] It is this function of CXCL12 that makes it a very important factor in carcinogenesis and the neovascularisation linked to tumour progression. [Kryczek I, Wei S, Keller E, Liu R, Zou W. Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis. Am J Physiol Cell Physiol. 2007 Mar;292(3):C987-95.]
As another role, CXCL12a alters also the
CXCL12 was shown to be expressend in many tissues in mice (including
brain, thymus, heart, lung, liver, kidney, spleenand bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. [Bleul et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382: 829-833, 1996.] This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor. [Balabanian et al. The chemokine SDF-1/CXCl12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem 280:35760-35766, 2005.] [Burns et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 203:2201-2213, 2006.]
The gene for CXCL12 is located on human
chromosome 10. [Deloukas et al. The DNA sequence and comparative analysis of human chromosome 10. Nature 429:375-381, 2004.] In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.
*cite journal | author=Kucia M, Reca R, Miekus K, "et al." |title=Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis |journal=Stem Cells |volume=23 |issue= 7 |pages= 879–94 |year= 2005 |pmid= 15888687 |doi= 10.1634/stemcells.2004-0342
*cite journal | author=Kryczek I, Wei S, Keller E, "et al." |title=Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis |journal=Am. J. Physiol., Cell Physiol. |volume=292 |issue= 3 |pages= C987–95 |year= 2007 |pmid= 16943240 |doi= 10.1152/ajpcell.00406.2006
*cite journal | author=Stellos K, Gawaz M |title=Platelets and stromal cell-derived factor-1 in progenitor cell recruitment |journal=Semin. Thromb. Hemost. |volume=33 |issue= 2 |pages= 159–64 |year= 2007 |pmid= 17340464 |doi= 10.1055/s-2007-969029
*cite journal | author=Arya M, Ahmed H, Silhi N, "et al." |title=Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration |journal=Tumour Biol. |volume=28 |issue= 3 |pages= 123–31 |year= 2007 |pmid= 17510563 |doi= 10.1159/000102979
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