AMPK通过下调CCL2抑制舌鳞状细胞癌肿瘤微环境中M2巨噬细胞的极化  

AMPK inhibits macrophage M2 polarization in TME through downregulating the expression of CCL2 in tongue carcinoma cells

作　　者：唐显帅 邹军荣 TANG Xianshuai;ZOU Junrong(Department of Pharmacy,Shandong Provincial Third Hospital,253301 Ji'nan,China;The First Affiliated Hospital of Gannan Medical University,Ganzhou)

机构地区：[1]山东省立第三医院药学部,济南253301 [2]赣南医学院第一附属医院

出　　处：《实用口腔医学杂志》2023年第6期796-803,共8页Journal of Practical Stomatology

基　　金：江西省自然科学基金(编号:20202BABL206031,20224BAB-216024);美捷登青年科学家创新基金(编号:MJR2020-1201)。

摘　　要：目的:探究单磷酸腺苷激酶(AMPK)在舌鳞状细胞癌(TSCC)中的作用及与肿瘤微环境(TME)巨噬细胞分化的关系。方法:免疫组化检测AMPK在舌癌组织的磷酸化水平及与患者预后的关系。多重免疫荧光检测AMPK的磷酸化水平与肿瘤微环境巨噬细胞极化的关系。通过条件性共培养,观察AMPK激活后,对单核细胞体外诱导成功率的影响。结果:免疫组织化学检测结果发现,在舌癌组织中AMPK磷酸化水平显著高于其癌旁组织。多重免疫荧光显示AMPK的磷酸化水平与M1型巨噬细胞浸润呈正相关,与M2型巨噬细胞浸润呈负相关。ELISA及体外条件性共培养实验提示肿瘤细胞AMPK激活后趋化因子(C-C基序)配体2(CCL2)的表达下降,促进巨噬细胞向M1极化,抑制M2极化。结论:AMPK可以通过下调舌癌细胞的CCL2的表达抑制TME中巨噬细胞的M2极化。Objective:To investigate the role of AMPK in tongue squamous cell carcinoma(TSCC)and its relationship with macrophage differentiation in tumor microenvironment(TME).Methods:Immunohistochemistry was used to detect the phosphorylation level of AMPK in tongue cancer tissues and its relationship with the prognosis of patients.The relationship between the phosphorylation level of AMPK and the polarization of macrophages in the TME was detected by multiplex immunofluorescence staining(mIF).Conditional co-culture was used to observe the effect of AMPK activation on the success rate of monocyte induction in vitro.Results:Immunohistochemical results showed that the phosphorylation level of AMPK was significantly higher in TSCC tissues than in adjacent tissues.mIF results showed that the phosphorylation level of AMPK was positively correlated with M1-type macrophage infiltration and negatively correlated with M2-type macrophage infiltration.ELISA and in vitro conditional co-culture experiments showed that the expression of CCL2 decreased after AMPK activation in tumor cells,which promoted the polarization of macrophages to M1 and inhibited the polarization of macrophages to M2.Conclusion:AMPK inhibits M2 polarization of macrophages in TME through downregulating the expression of CCL2 in tongue carcinoma cells.

关 键 词：单磷酸腺苷激酶 肿瘤微环境 M2型巨噬细胞极化 CCL2 

分 类 号：R739.8[医药卫生—肿瘤]