Song Sinuo, Zhao Yunping, Fu Tianyu, Fan Yunfei, Tang Jie, Wang Xiaoxing, Liu Chao, Chen Xiaobo
Department of Medical management, 920th Hospital of Joint Logistics Support Force, Kunming, Yunnan, P.R. China.
Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
Immunol Invest. 2023 Jan;52(1):20-34. doi: 10.1080/08820139.2022.2115379. Epub 2022 Sep 14.
Macrophages are one of the most important immunoinflammatory cell populations in the tumor microenvironment (TME). In this study, we preliminarily investigated the upstream pathway of M2 macrophage polarization affecting lung cancer progression.
Bioinformatics analysis was used to evaluate genes closely associated with lung adenocarcinoma and their relationship with immune cells. THP-1 monocytes were induced into M2 macrophages. The expression of markers in M2 macrophages was detected by quantitative reverse transcription-PCR (qRT-PCR), enzyme linked immunosorbent assay (ELISA), and flow cytometry. The effects of neutrophil elastase (ELANE)-mediated M2 macrophages on lung cancer cell proliferation, migration and invasion and tumor growth were investigated by in vitro and in vivo experiments after co-culture of macrophage conditioned medium (CM) and lung cancer cell lines A549 and H1299. The PTEN protein expression was detected by Western blotting.
ELANE was significantly positively correlated with M2 macrophages. ELANE up-regulated the expression of the M2 macrophage markers CD206, CCL22, IL-10 and CCL18 and increased the proportion of CD206+ macrophages. Compared with M0-CM, M2-CM promoted cell proliferation, migration, and invasion, and (M2+ELANE)-CM further enhanced this effect. In vivo, ELANE promoted M2 macrophage-induced tumor growth in lung cancer mice model. In vitro experiments showed that ELANE can down-regulate the expression of PTEN and promote the polarization of M2 macrophages.
ELANE promotes the polarization of M2 macrophages by down-regulating PTEN, thus promoting cell proliferation, migration, and invasion in vitro and growth of lung cancer cells in vivo.
巨噬细胞是肿瘤微环境（TME）中最重要的免疫炎症细胞群体之一。在本研究中，我们初步探究了影响肺癌进展的M2巨噬细胞极化的上游通路。
采用生物信息学分析评估与肺腺癌密切相关的基因及其与免疫细胞的关系。将THP-1单核细胞诱导为M2巨噬细胞。通过定量逆转录聚合酶链反应（qRT-PCR）、酶联免疫吸附测定（ELISA）和流式细胞术检测M2巨噬细胞中标志物的表达。在巨噬细胞条件培养基（CM）与肺癌细胞系A549和H1299共培养后，通过体外和体内实验研究中性粒细胞弹性蛋白酶（ELANE）介导的M2巨噬细胞对肺癌细胞增殖、迁移、侵袭及肿瘤生长的影响。通过蛋白质免疫印迹法检测PTEN蛋白表达。
ELANE与M2巨噬细胞显著正相关。ELANE上调M2巨噬细胞标志物CD206、CCL22、IL-10和CCL18的表达，并增加CD206+巨噬细胞的比例。与M0-CM相比，M2-CM促进细胞增殖、迁移和侵袭，且（M2+ELANE）-CM进一步增强了这种作用。在体内，ELANE促进肺癌小鼠模型中M2巨噬细胞诱导的肿瘤生长。体外实验表明，ELANE可下调PTEN的表达并促进M2巨噬细胞极化。
ELANE通过下调PTEN促进M2巨噬细胞极化，从而在体外促进细胞增殖、迁移和侵袭，并在体内促进肺癌细胞生长。
