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Regulation of the chemokine receptor CXCR4 by hypoxia

  1. Author:
    Schioppa, T.
    Uranchimeg, B.
    Saccani, A.
    Biswas, S. K.
    Doni, A.
    Rapisarda, A.
    Bernasconi, S.
    Saccani, S.
    Nebuloni, M.
    Vago, L.
    Mantovani, A.
    Melillo, G.
    Sica, A.

  2. Author Address

    Mario Negri Inst Pharmacol Res, Via Eritrea 62, I-20157 Milan, Italy Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy State Univ Milan, Inst Pathol, Ctr Eccellenza Innovaz Diangnost & Terapeut, I-20133 Milan, Italy Biomed Res Inst, CH-6500 Bellinzona, Switzerland Univ Milan, Dept Clin Sci L Sacco, Inst Pathol, I-20157 Milan, Italy NCI, Sci Applicat Int Corp Frederick Inc, Tumor Hypoxia Lab, Dev Therapeut Program, Frederick, MD 21702 USA Sica A Mario Negri Inst Pharmacol Res, Via Eritrea 62, I-20157 Milan, Italy
    1. Year: 2003
  2. Journal: Journal of Experimental Medicine
    1. 198
    2. 9
    3. Pages: 1391-1402
  4. Type of Article: Article
  1. 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 (CXCP4), 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 micro enviroriments.

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