Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI:10.1007/s00262-024-03866-4
Guiyu Kang, Hui Song, Lei Bo, Qi Liu, Qiang Li, Jingtan Li, Pan Pan, Jingting Wang, Yanfei Jia, Haiji Sun, Xiaoli Ma
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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.

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尼古丁通过α5-nAChR/SOX2/CSF-1轴促进肺腺癌M2巨噬细胞极化
α5-烟碱乙酰胆碱受体(α5-nAChR)在肺腺癌(LUAD)中起着至关重要的作用。然而,人们对α5-nAChR如何影响肺腺癌的认识并不全面。α5-nAChR通过靶向STAT3/SOX2/CSF-1信号,在共培养系统中调控单核细胞向M2巨噬细胞的分化。在共培养培养基中,α5-nAChR 通过 SOX2/CSF-1 信号介导巨噬细胞介导的 LUAD 细胞迁移。在小鼠 LUAD 模型和临床样本中验证了 α5-nAChR、SOX2 和 M2 表型肿瘤相关巨噬细胞(TAMs)的相关性。尼古丁诱导的SOX2表达是由α5-nAChR通过STAT3介导的。此外,SOX2介导的巨噬细胞集落刺激因子(CSF-1)的表达也有助于LUAD在体外的进展。此外,α5-nAChR 的表达与 pSTAT3、SOX2 和 M2 巨噬细胞标记 CD206 的表达密切相关,而与体内 M1 巨噬细胞标记 CD86 的表达呈负相关。研究表明,在尼古丁相关 LUAD 中,M2 巨噬细胞是由新的α5-nAChR /SOX2/CSF-1 轴介导的,这是一种潜在的癌症治疗策略。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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