Regulation of the Chemokine Receptor CXCR4 by Hypoxia

Tiziana Schioppa, Badarch Uranchimeg, Alessandra Saccani, Subhra K. Biswas, Andrea Doni, Annamaria Rapisarda, Sergio Bernasconi, Simona Saccani, Manuela Nebuloni, Luca Vago, Alberto Mantovani, Giovanni Melillo, Antonio Sica

Research output: Contribution to journalArticlepeer-review


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 α and transcript stabilization. In a relay multistep navigation process, the Hyp-Hyp-inducible factor 1 α-CXCR4 pathway may regulate trafficking in and out of hypoxic tissue microenvironments.

Original languageEnglish
Pages (from-to)1391-1402
Number of pages12
JournalJournal of Experimental Medicine
Issue number9
Publication statusPublished - Nov 3 2003


  • Cell migration
  • Hypoxia-inducible factor 1 (HIF-1)
  • Low oxygen concentration
  • SDF-1/CXCL12 receptor (CXCR4)

ASJC Scopus subject areas

  • Immunology


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