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PMID: 14597738 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of the chemokine receptor CXCR4 by hypoxia.

The Journal of experimental medicine ·Vol. 198 ·No. 9 ·2003-11-03 ·Pages 1391-402

Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, Bernasconi S, Saccani S, Nebuloni M, Vago L, Mantovani A, Melillo G, Sica A

Abstract

Cell adaptation to hypoxia (Hyp) requires activation of transcriptional programs that coordinate expression of genes involved in oxygen delivery (via angiogenesis) and metabolic adaptation (via glycolysis). Here, we describe that oxygen availability is a determinant parameter in the setting of chemotactic responsiveness to stromal-derived factor 1 (CXCL12). Low oxygen concentration induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCR4), in different cell types (monocytes, monocyte-derived macrophages, tumor-associated macrophages, endothelial cells, and cancer cells), which is paralleled by increased chemotactic responsiveness to its specific ligand. CXCR4 induction by Hyp is dependent on both activation of the Hyp-inducible factor 1 alpha and transcript stabilization. In a relay multistep navigation process, the Hyp-Hyp-inducible factor 1 alpha-CXCR4 pathway may regulate trafficking in and out of hypoxic tissue microenvironments.

MeSH Terms
Animals Base Sequence Cell Hypoxia Cells, Cultured DNA Primers Endothelium, Vascular/cytology,metabolism Humans Mice Phagocytes/metabolism RNA, Messenger/genetics Receptors, CXCR4/genetics,metabolism,physiology
Chemicals
DNA Primers RNA, Messenger Receptors, CXCR4
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Schioppa Tiziana
Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milan, Italy.
Uranchimeg Badarch
Saccani Alessandra
Biswas Subhra K
Doni Andrea
Rapisarda Annamaria
Bernasconi Sergio
Saccani Simona
Nebuloni Manuela
Vago Luca
Mantovani Alberto
Melillo Giovanni
Sica Antonio
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20030267
Published
2003-11-03
Pages
1391-402
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2194248
Subset
IM
Grants
NCI NIH HHS · N01CO12400 · United States
NCI NIH HHS · N01-CO-12400 · United States
External Links
PubMed source DOI: 10.1084/jem.20030267 PMC Full Text View journal details
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