Journal
LEUKEMIA
Volume 20, Issue 11, Pages 1915-1924Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2404357
Keywords
CXCR4; VSEL; primordial germ cells; organogenesis; regeneration; metastasis
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Funding
- NCI NIH HHS [R01 CA106281-01] Funding Source: Medline
- NIDDK NIH HHS [R01 DK074720-01] Funding Source: Medline
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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.
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