HIF-α/MIF and NF-κB/IL-6 Axes Contribute to the Recruitment of CD11b+Gr-1+ Myeloid Cells in Hypoxic Microenvironment of HNSCC
| Autor: | Jian Jiang, Xin-hua Liang, Longjiang Li, Min Zheng, Ya-ling Tang, Wei Chen, Yun-long Fan, Zhengge Lei, Kai-de Li, Xiang-rui Ma, Ning Geng, Xiaoyi Wang, Ling Li, Guiquan Zhu |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
medicine.medical_specialty Myeloid Cellular differentiation Mice Nude Biology lcsh:RC254-282 Cell Line Tumor Internal medicine Tumor Microenvironment medicine Animals Humans Myeloid Cells Macrophage Migration-Inhibitory Factors Protein kinase B PI3K/AKT/mTOR pathway Tumor microenvironment CD11b Antigen Neovascularization Pathologic Interleukin-6 Chemotaxis NF-kappa B Cell Differentiation Cell migration Hypoxia-Inducible Factor 1 alpha Subunit lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Head and neck squamous-cell carcinoma Cell Hypoxia Intramolecular Oxidoreductases medicine.anatomical_structure Endocrinology Head and Neck Neoplasms Carcinoma Squamous Cell Cancer research Receptors Chemokine Macrophage migration inhibitory factor Neoplasm Transplantation Signal Transduction Research Article |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 16, Iss 2, Pp 168-179 (2014) |
| ISSN: | 1476-5586 |
| Popis: | CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF) and interleukin-6 (IL-6) by head and neck squamous cell carcinoma (HNSCC) cells. Hypoxia-inducible factor-1α (HIF-1α)- and HIF-2α-dependent MIF regulated chemotaxis, differentiation, and pro-angiogenic function of CD11b+Gr-1+ myeloid cells through binding to CD74/CXCR2, and CD74/CXCR4 complexes, and then activating p38/mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinases (PI3K)/AKT signaling pathways. Knockdown (KD) of HIF-1α and HIF-2α in HNSCC cells decreased MIF level but failed to inhibit the CD11b+Gr-1+ myeloid cell migration, because HIF-1α/2α KD enhanced nuclear factor κB (NF-κB) activity that increased IL-6 secretion. Simultaneously blocking NF-κB and HIF-1α/HIF-2α had better inhibitory effect on CD11b+Gr-1+ myeloid cell recruitment in the hypoxic zone than individually silencing HIF-1α/2α or NF-κB. In conclusion, the interaction between HIF-α/MIF and NF-κB/IL-6 axes plays an important role in the hypoxia-induced accumulation of CD11b+Gr-1+ myeloid cells and tumor growth in HNSCC. |
| Databáze: | OpenAIRE |
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