M2型巨噬细胞在肝癌的表达意义及与p-STAT3、STAT3的关系  

Significance of M2 macrophages in hepatocellular carcinoma and its correlation with p-STAT3 and STAT3

作　　者：潘晶晶[1] 葛勇胜[1,2] 许戈良[1,2] 李建生[1,2] 荚卫东[1,2] 马金良[1,2] 余继海[1,2] 刘文斌[1,2] 张传海[1,2] 任维年[1,2] 

机构地区：[1]安徽医科大学附属省立医院肝脏外科,合肥230001 [2]安徽医科大学附属省立医院肝胆胰外科安徽省重点实验室,合肥230001

出　　处：《安徽医科大学学报》2013年第10期1147-1151,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金面上项目(编号:81272398);安徽高校省自然科学研究项目(编号:KJ2012Z179)

摘　　要：目的研究M2型巨噬细胞在肝癌中的表达及临床意义及与磷酸化信号转录活化因子3(p-STAT3)、信号转录活化因子3(STAT3)的关系。方法采用免疫组织化学双染方法检测79例肝癌组织标本中M2型巨噬细胞(CD68、CD163)及单染检测p-STAT3、STAT3的表达,分析其与临床病理参数之间的关系。从健康人外周血中分离单核细胞,用白介素4(IL-4)和IL-13极化刺激成M2型巨噬细胞。分别与人肝癌细胞株SMMC7721、HepG2在Transwell小室中进行共培养48 h,未与M2型巨噬细胞共培养的肝癌细胞设置为空白对照组。Western blot法检测肝癌细胞株中p-STAT3、STAT3蛋白与空白对照组的表达差异。结果肝癌组织中M2型巨噬细胞浸润与TNM分期相关(P<0.05)。在共培养实验中,与M2型巨噬细胞共培养的SMMC7721,HepG2与实验对照组比较,细胞中p-STAT3蛋白表达明显增加(P<0.01),而STAT3蛋白表达无明显改变。结论 M2型巨噬细胞与肝癌恶性行为相关,可能通过上调p-STAT3的表达进而推动肝癌的发生发展。Objective To investigate expression and clinical significances of M2 macrophages in hepatocellular carcinoma （HCC） and the relationship between M2 macrophages and phosphorylated signal transducer and activator of transcription 3 （ p-STAT3 ） and signal transducer and activator of transcription 3 （ STAT3 ）. Methods The expression of M2 maerophages was evaluated by double staining of CD68 and CD163 ; p-STAT3, STAT3 expression was assessed by immunohistochemistry. The association of M2 macrophages with clinic parameters was evaluated. Monocytes were isolated from peripheral blood of healthy volunteers and then monocytes were polarized to be M2 macrophages by IL-4 and IL-13 stimulation. SMMC7721 and HepG2 cells were co-cultured with M2 macrophages in a Transwell system for 48 hours, respectively ; HCC cells without co-culture with M2 macrophages were performed as controls. The expression of p-STAT3 and STAT-3 of HCC cells with or without co-culture with M2 macrophages were examined by western blot. Results High infiltration of M2 macrophages positively correlated with TNM stages （P 〈0.05）. In the co-cuhure experiment, the expression of p-STAT3 of HepG2 and SMMC7721 was significantly up-regulated upon co-culture with M2 macrophages （P 〈0. 01 ）, but the expression of STAT3 was not significantly altered upon co-culture with M2 macrophages compared with controls. Conclusion M2-polarized macrophages are associated with malignant behavior in HCCs, whose pro-tumor effect may be partly due to the phosphorylation of STAT3.

关 键 词：肝细胞肝癌 M2型巨噬细胞 信号转录活化因子3 磷酸化信号转录活化因子3 转移 

分 类 号：R735.7[医药卫生—肿瘤]