Regulation of the Chemokine Receptor CXCR4 by Hypoxia
- Schioppa, Tiziana Istituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
- Uranchimeg, Badarch Development Therapeutic Program, Tumor Hypoxia Laboratory, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702
- Saccani, Alessandra Istituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
- Biswas, Subhra K. Istituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
- Doni, Andrea Istituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
- Rapisarda, Annamaria Development Therapeutic Program, Tumor Hypoxia Laboratory, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702
- Bernasconi, Sergio Istituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
- Saccani, Simona Institute for Research in Biomedicine, Bellinzona, CH6500 Switzerland
- Nebuloni, Manuela Institute of Pathology, Department of Clinical Sciences “L. Sacco,” University of Milan, 20157 Milan, Italy
- Vago, Luca Institute of Pathology, Department of Clinical Sciences “L. Sacco,” University of Milan, 20157 Milan, Italy
- Mantovani, Alberto Centro di Eccellenza per l'Innovazione Diangnostica e Terapeutica, Institute of Pathology, State University of Milan, 20133 Milan, Italy
- Melillo, Giovanni Development Therapeutic Program, Tumor Hypoxia Laboratory, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702
- Sica, Antonio Istituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
- 2003-11-3
Published in:
- Journal of Experimental Medicine. - Rockefeller University Press. - 2003, vol. 198, no. 9, p. 1391-1402
English
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.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1084/jem.20030267
- ISSN 1540-9538
- Persistent URL
- https://sonar.rero.ch/global/documents/62964
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