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PMID: 15339043 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion.

Journal of molecular histology ·Vol. 35 ·No. 3 ·2004-03-00 ·Pages 233-45

Kucia M, Jankowski K, Reca R, Wysoczynski M, Bandura L, Allendorf DJ, Zhang J, Ratajczak J, Ratajczak MZ

Abstract

Chemokines, small pro-inflammatory chemoattractant cytokines, that bind to specific G-protein-coupled seven-span transmembrane receptors present on plasma membranes of target cells are the major regulators of cell trafficking. In addition some chemokines have been reported to modulate cell survival and growth. Moreover, compelling evidence is accumulating that cancer cells may employ several mechanisms involving chemokine-chemokine receptor axes during their metastasis that also regulate the trafficking of normal cells. Of all the chemokines, stromal-derived factor-1 (SDF-1), an alpha-chemokine that binds to G-protein-coupled CXCR4, plays an important and unique role in the regulation of stem/progenitor cell trafficking. First, SDF-1 regulates the trafficking of CXCR4+ haemato/lymphopoietic cells, their homing/retention in major haemato/lymphopoietic organs and accumulation of CXCR4+ immune cells in tissues affected by inflammation. Second, CXCR4 plays an essential role in the trafficking of other tissue/organ specific stem/progenitor cells expressing CXCR4 on their surface, e.g., during embryo/organogenesis and tissue/organ regeneration. Third, since CXCR4 is expressed on several tumour cells, these CXCR4 positive tumour cells may metastasize to the organs that secrete/express SDF-1 (e.g., bones, lymph nodes, lung and liver). SDF-1 exerts pleiotropic effects regulating processes essential to tumour metastasis such as locomotion of malignant cells, their chemoattraction and adhesion, as well as plays an important role in tumour vascularization. This implies that new therapeutic strategies aimed at blocking the SDF-1-CXCR4 axis could have important applications in the clinic by modulating the trafficking of haemato/lymphopoietic cells and inhibiting the metastatic behaviour of tumour cells as well. In this review, we focus on a role of the SDF-1-CXCR4 axis in regulating the metastatic behaviour of tumour cells and discuss the molecular mechanisms that are essential to this process.

MeSH Terms
Animals Cell Adhesion/physiology Cell Movement/physiology Chemokine CXCL12 Chemokines, CXC/metabolism Chemotaxis/physiology Humans Neoplasm Metastasis/pathology,physiopathology Neoplasms/metabolism,pathology Receptors, CXCR4/metabolism Signal Transduction
Chemicals
CXCL12 protein, human Chemokine CXCL12 Chemokines, CXC Receptors, CXCR4
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kucia Magda
Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, KY 40202, USA.
Jankowski Kacper
Reca Ryan
Wysoczynski Marcin
Bandura Laura
Allendorf Daniel J
Zhang Jin
Ratajczak Janina
Ratajczak Mariusz Z
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Article Info
Journal
Journal of molecular histology
Abbr.
J Mol Histol
ISSN
1567-2379
DOI
10.1023/b:hijo.0000032355.66152.b8
Published
2004-03-00
Pages
233-45
Language
English
Region
Netherlands
NLM ID
101193653
Subset
IM
Grants
NHLBI NIH HHS · R01 HL61796-01 · United States
External Links
PubMed source DOI: 10.1023/b:hijo.0000032355.66152.b8 View journal details
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