期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 198, 期 9, 页码 1391-1402出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030267
关键词
cell migration; SDF-1/CXCL12 receptor (CXCR4); low oxygen concentration; hypoxia-inducible factor 1 (HIF-1)
资金
- NCI NIH HHS [N01-CO-12400, N01CO12400] Funding Source: Medline
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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