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

Leukemia volume 20, pages 1915–1924 (2006)Cite this article

Abstract

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 α-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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Acknowledgements

This work was supported by an NIH Grant R01 CA106281-01 and R01 DK074720-01 to MZR.

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Authors and Affiliations

  1. Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    M Z Ratajczak, E Zuba-Surma, M Kucia, R Reca & J Ratajczak

  2. Third Division of Cardiology, Silesian School of Medicine, Katowice, Poland

    W Wojakowski

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  1. M Z Ratajczak
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  2. E Zuba-Surma
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  3. M Kucia
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Correspondence to M Z Ratajczak.

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Ratajczak, M., Zuba-Surma, E., Kucia, M. et al. The pleiotropic effects of the SDF-1–CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia 20, 1915–1924 (2006). https://doi.org/10.1038/sj.leu.2404357

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