Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma
Abstract α5-nicotinic acetylcholine receptor (α5-nAChR) plays a vital part in lung adenocarcinoma (LUAD). However, it is not comprehensively understood that how the α5-nAChR affects LUAD. Through diverse bioinformatics analyses and immunohistochemistry, the expressions of α5-nAChR and SOX2 as well a...
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03866-4 |
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| author | Guiyu Kang Hui Song Lei Bo Qi Liu Qiang Li Jingtan Li Pan Pan Jingting Wang Yanfei Jia Haiji Sun Xiaoli Ma |
| author_facet | Guiyu Kang Hui Song Lei Bo Qi Liu Qiang Li Jingtan Li Pan Pan Jingting Wang Yanfei Jia Haiji Sun Xiaoli Ma |
| author_sort | Guiyu Kang |
| collection | DOAJ |
| description | Abstract α5-nicotinic acetylcholine receptor (α5-nAChR) plays a vital part in lung adenocarcinoma (LUAD). However, it is not comprehensively understood that how the α5-nAChR affects LUAD. Through diverse bioinformatics analyses and immunohistochemistry, the expressions of α5-nAChR and SOX2 as well as their relations were dissected. α5-nAChR regulated the differentiation of monocytes into M2 macrophages by targeting the STAT3/SOX2/CSF-1 signaling in the coculture system by western blotting and ChIP. α5-nAChR-mediated macrophage-mediated LUAD cell migration via SOX2/CSF-1 signaling in the cocultured medium. Correlations of α5-nAChR, SOX2 and M2 phenotype tumor-associated macrophages (TAMs) were validated in mouse LUAD models and clinical samples. α5-nAChR expression was connected to SOX2 expression, smoking and bad prognosis of LUAD among clinical samples. Nicotine-induced SOX2 expression was mediated by α5-nAChR via STAT3. Additionally, SOX2-mediated macrophage colony-stimulating factor (CSF-1) expression contributed to LUAD progression in vitro. Furthermore, α5-nAChR expression was strongly linked to pSTAT3, SOX2 and M2 macrophage marker CD206 expression and negatively correlated with M1 macrophage marker CD86 expression in vivo. It is indicated that M2 macrophages are mediated by the new α5-nAChR /SOX2/CSF-1 axis in nicotine-related LUAD, which is a potential therapeutic strategy for cancer. |
| format | Article |
| id | doaj-art-7b93b0fb9219448599ab9625180726b2 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-7b93b0fb9219448599ab9625180726b22025-02-02T12:26:40ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111610.1007/s00262-024-03866-4Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinomaGuiyu Kang0Hui Song1Lei Bo2Qi Liu3Qiang Li4Jingtan Li5Pan Pan6Jingting Wang7Yanfei Jia8Haiji Sun9Xiaoli Ma10Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityDepartment of Cardiology, Central Hospital Affiliated to Shandong First Medical UniversityDepartment of Clinical Laboratory, The 960 Hospital of PLAResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityCollege of Life Science, Shandong Normal UniversityResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical UniversityAbstract α5-nicotinic acetylcholine receptor (α5-nAChR) plays a vital part in lung adenocarcinoma (LUAD). However, it is not comprehensively understood that how the α5-nAChR affects LUAD. Through diverse bioinformatics analyses and immunohistochemistry, the expressions of α5-nAChR and SOX2 as well as their relations were dissected. α5-nAChR regulated the differentiation of monocytes into M2 macrophages by targeting the STAT3/SOX2/CSF-1 signaling in the coculture system by western blotting and ChIP. α5-nAChR-mediated macrophage-mediated LUAD cell migration via SOX2/CSF-1 signaling in the cocultured medium. Correlations of α5-nAChR, SOX2 and M2 phenotype tumor-associated macrophages (TAMs) were validated in mouse LUAD models and clinical samples. α5-nAChR expression was connected to SOX2 expression, smoking and bad prognosis of LUAD among clinical samples. Nicotine-induced SOX2 expression was mediated by α5-nAChR via STAT3. Additionally, SOX2-mediated macrophage colony-stimulating factor (CSF-1) expression contributed to LUAD progression in vitro. Furthermore, α5-nAChR expression was strongly linked to pSTAT3, SOX2 and M2 macrophage marker CD206 expression and negatively correlated with M1 macrophage marker CD86 expression in vivo. It is indicated that M2 macrophages are mediated by the new α5-nAChR /SOX2/CSF-1 axis in nicotine-related LUAD, which is a potential therapeutic strategy for cancer.https://doi.org/10.1007/s00262-024-03866-4α5-nicotinic acetylcholine receptor (α5-nAChR)SOX2Macrophage colony-stimulating factor (CSF-1)M1/M2 polarizationLUAD |
| spellingShingle | Guiyu Kang Hui Song Lei Bo Qi Liu Qiang Li Jingtan Li Pan Pan Jingting Wang Yanfei Jia Haiji Sun Xiaoli Ma Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma Cancer Immunology, Immunotherapy α5-nicotinic acetylcholine receptor (α5-nAChR) SOX2 Macrophage colony-stimulating factor (CSF-1) M1/M2 polarization LUAD |
| title | Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma |
| title_full | Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma |
| title_fullStr | Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma |
| title_full_unstemmed | Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma |
| title_short | Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma |
| title_sort | nicotine promotes m2 macrophage polarization through α5 nachr sox2 csf 1 axis in lung adenocarcinoma |
| topic | α5-nicotinic acetylcholine receptor (α5-nAChR) SOX2 Macrophage colony-stimulating factor (CSF-1) M1/M2 polarization LUAD |
| url | https://doi.org/10.1007/s00262-024-03866-4 |
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