The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis

Leukemia. 2006 Nov;20(11):1915-24. doi: 10.1038/sj.leu.2404357. Epub 2006 Aug 10.


Proper response of normal stem cells (NSC) to motomorphogens and chemoattractants plays a pivotal role in organ development and renewal/regeneration of damaged tissues. Similar chemoattractants may also regulate metastasis of cancer stem cells (CSC). Growing experimental evidence indicates that both NSC and CSC express G-protein-coupled seven-transmembrane span receptor CXCR4 and respond to its specific ligand alpha-chemokine stromal derived factor-1 (SDF-1), which is expressed by stroma cells from different tissues. In addition, a population of very small embryonic-like (VSEL) stem cells that express CXCR4 and respond robustly to an SDF-1 gradient was recently identified in adult tissues. VSELs express several markers of embryonic and primordial germ cells. It is proposed that these cells are deposited early in the development as a dormant pool of embryonic/pluripotent NSC. Expression of both CXCR4 and SDF-1 is upregulated in response to tissue hypoxia and damage signal attracting circulating NSC and CSC. Thus, pharmacological modulation of the SDF-1-CXCR4 axis may lead to the development of new therapeutic strategies to enhance mobilization of CXCR4+ NSC and their homing to damaged organs as well as inhibition of the metastasis of CXCR4+ cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Chemokine CXCL12
  • Chemokines, CXC / physiology*
  • Humans
  • Neoplasms / physiopathology*
  • Organogenesis / physiology*
  • Receptors, CXCR4 / physiology*
  • Regeneration / physiology*


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Receptors, CXCR4