Stromal cell-derived factor 1

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Protein CXCL12 PDB 1a15.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases CXCL12, IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1, C-X-C motif chemokine ligand 12
External IDs MGI: 103556 HomoloGene: 128606 GeneCards: 6387
RNA expression pattern
PBB GE CXCL12 203666 at tn.png

PBB GE CXCL12 209687 at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 10: 44.37 – 44.39 Mb Chr 6: 117.17 – 117.18 Mb
PubMed search [1] [2]
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The stromal cell-derived factor 1 (SDF1) also known as C-X-C motif chemokine 12 (CXCL12) is a chemokine protein that in humans is encoded by the CXCL12 gene.

Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the chemokine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The chemokines are characterized by the presence of 4 conserved cysteines that form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, the cysteine residues are adjacent to each other. In the CXC subfamily, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group.[3]


SDF-1 is produced in two forms, SDF-1α/CXCL12a and SDF-1β/CXCL12b, by alternate splicing of the same gene.[4] 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 chemotactic for lymphocytes.[5][6][7][8] During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow and the formation of large blood vessels. It has been also shown that SDF1 signalling regulates the expression of CD20 on B cells.[9] Mice that 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 (EPCs) from the bone marrow through a CXCR4 dependent mechanism.[10] It is this function of CXCL12 that makes it a very important factor in carcinogenesis and the neovascularisation linked to tumour progression.[11] CXCL12 also has a role in tumor metastasis where cancer cells that express the receptor CXCR4 are attracted to metastasis target tissues that release the ligand, CXCL12.[12] In breast cancer, however, increased expression of CXCL12 determines a reduced risk of distant metastasis.[13][14]

In 2011, CXCL12 was shown to be responsible for recruiting macrophages to breast tumours in mice in response to the experimental anti-cancer drug combretastatin A-4 phosphate, which damages tumour blood vessels. This macrophage recruitment is believed to stimulate tumour blood vessel growth, counteracting the effects of the drug.

Blocking CXCR4, the receptor for CXCL12, with Plerixafor (AMD-3100) increased the effectiveness of combretastatin in a mouse model of breast cancer, it is presumed by preventing macrophages from being recruited to tumours.[15][16] Plerixafor also reduces CD20 expression on B cells. [17]

CXCL12 is expressed in the area of inflammatory bone destruction. It is chemotactic for mesenchymal stem cells and mediates their suppressive effect on osteoclastogenesis.[18]


By blocking CXCR4, a major coreceptor for HIV-1 entry, CXCL12 acts as an endogenous inhibitor of CXCR4-tropic HIV-1 strains.[19] CXCL12 was shown to be expressed in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).


The receptor for this chemokine is CXCR4, which was previously called LESTR or fusin.[20] This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 may also bind the CXCR7 receptor.[21][22][23]


The gene for CXCL12 is located on human chromosome 10.[24][25] In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ "Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)". 
  4. ^ De La Luz Sierra M, Yang F, Narazaki M, Salvucci O, Davis D, Yarchoan R, Zhang HH, Fales H, Tosato G (April 2004). "Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity". Blood. 103 (7): 2452–9. doi:10.1182/blood-2003-08-2857. PMID 14525775. 
  5. ^ Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA (September 1996). "A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)". The Journal of Experimental Medicine. 184 (3): 1101–9. doi:10.1084/jem.184.3.1101. PMC 2192798free to read. PMID 9064327. 
  6. ^ Ara T, Nakamura Y, Egawa T, Sugiyama T, Abe K, Kishimoto T, Matsui Y, Nagasawa T (April 2003). "Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1)". Proceedings of the National Academy of Sciences of the United States of America. 100 (9): 5319–23. doi:10.1073/pnas.0730719100. PMC 154343free to read. PMID 12684531. 
  7. ^ Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS (August 2003). "Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy". Lancet. 362 (9385): 697–703. doi:10.1016/S0140-6736(03)14232-8. PMID 12957092. 
  8. ^ Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA (August 1998). "Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice". Proceedings of the National Academy of Sciences of the United States of America. 95 (16): 9448–53. doi:10.1073/pnas.95.16.9448. PMC 21358free to read. PMID 9689100. 
  9. ^ Pavlasova G, Borsky M, Seda V, Cerna K, Osickova J, Doubek M, Mayer J, Calogero R, Trbusek M, Pospisilova S, Davids MS, Kipps TJ, Brown JR, Mraz M (August 2016). "Ibrutinib inhibits CD20 up-regulation on CLL B cells mediated by the CXCR4/SDF-1 axis". Blood. doi:10.1182/blood-2016-04-709519. PMID 27480113. 
  10. ^ Zheng H, Fu G, Dai T, Huang H (September 2007). "Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway". Journal of Cardiovascular Pharmacology. 50 (3): 274–80. doi:10.1097/FJC.0b013e318093ec8f. PMID 17878755. 
  11. ^ Kryczek I, Wei S, Keller E, Liu R, Zou W (March 2007). "Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis". American Journal of Physiology. Cell Physiology. 292 (3): C987–95. doi:10.1152/ajpcell.00406.2006. PMID 16943240. 
  12. ^ Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A (March 2001). "Involvement of chemokine receptors in breast cancer metastasis". Nature. 410 (6824): 50–6. doi:10.1038/35065016. PMID 11242036. 
  13. ^ Mirisola V, Zuccarino A, Bachmeier BE, Sormani MP, Falter J, Nerlich A, Pfeffer U (September 2009). "CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival". European Journal of Cancer. 45 (14): 2579–87. doi:10.1016/j.ejca.2009.06.026. PMID 19646861. 
  14. ^ Wendt MK, Cooper AN, Dwinell MB (February 2008). "Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells". Oncogene. 27 (10): 1461–71. doi:10.1038/sj.onc.1210751. PMID 17724466. 
  15. ^ Welford AF, Biziato D, Coffelt SB, Nucera S, Fisher M, Pucci F, Di Serio C, Naldini L, De Palma M, Tozer GM, Lewis CE (May 2011). "TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice". The Journal of Clinical Investigation. 121 (5): 1969–73. doi:10.1172/JCI44562. PMC 3083764free to read. PMID 21490397. 
  16. ^ [1], Cancer Research UK blog.
  17. ^ . PMID 27480113.  Missing or empty |title= (help)
  18. ^ Takano T, Li YJ, Kukita A, Yamaza T, Ayukawa Y, Moriyama K, Uehara N, Nomiyama H, Koyano K, Kukita T (March 2014). "Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis". Laboratory Investigation; A Journal of Technical Methods and Pathology. 94 (3): 286–96. doi:10.1038/labinvest.2013.152. PMID 24395111. 
  19. ^ Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier JL, Arenzana-Seisdedos F, Schwartz O, Heard JM, Clark-Lewis I, Legler DF, Loetscher M, Baggiolini M, Moser B (August 1996). "The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1". Nature. 382 (6594): 833–5. doi:10.1038/382833a0. PMID 8752281. 
  20. ^ Bleul CC, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer TA (August 1996). "The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry". Nature. 382 (6594): 829–33. doi:10.1038/382829a0. PMID 8752280. 
  21. ^ Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F (October 2005). "The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes". The Journal of Biological Chemistry. 280 (42): 35760–6. doi:10.1074/jbc.M508234200. PMID 16107333. 
  22. ^ Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ (September 2006). "A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development". The Journal of Experimental Medicine. 203 (9): 2201–13. doi:10.1084/jem.20052144. PMC 2118398free to read. PMID 16940167. 
  23. ^ Cruz-Orengo L, Holman DW, Dorsey D, Zhou L, Zhang P, Wright M, McCandless EE, Patel JR, Luker GD, Littman DR, Russell JH, Klein RS (February 2011). "CXCR7 influences leukocyte entry into the CNS parenchyma by controlling abluminal CXCL12 abundance during autoimmunity". The Journal of Experimental Medicine. 208 (2): 327–39. doi:10.1084/jem.20102010. PMC 3039853free to read. PMID 21300915. 
  24. ^ Shirozu M, Nakano T, Inazawa J, Tashiro K, Tada H, Shinohara T, Honjo T (August 1995). "Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene". Genomics. 28 (3): 495–500. doi:10.1006/geno.1995.1180. PMID 7490086. 
  25. ^ Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, et al. (May 2004). "The DNA sequence and comparative analysis of human chromosome 10". Nature. 429 (6990): 375–81. doi:10.1038/nature02462. PMID 15164054. 

Further reading[edit]