TGF-β在肝细胞癌转移中的作用  

Role of TGF-β in metastasis of hepatocellular carcinoma

作　　者：张颖慧[1] 董向前[2] 邹玉[1] 乌剑利[3] 白丽萍[1] 刘晶华[1] 王敏[1] 

机构地区：[1]云南省第二人民医院消化内科,云南省昆明市650021 [2]昆明医科大学第一附属医院消化内科,云南省昆明市650032 [3]华中科技大学同济医学院附属同济医院肝脏外科,湖北省武汉市430030

出　　处：《世界华人消化杂志》2013年第25期2508-2514,共7页World Chinese Journal of Digestology

摘　　要：目的:探讨外周血中调节性T细胞来源的转化生长因子(transforming growth factor-β,TGF-β)在肝细胞癌转移中的作用及临床意义.方法:选择原发性肝细胞癌无远端脏器转移患者48例,伴有远端脏器转移的患者32例(其中肺部转移17例、脑部转移15例),健康对照54例,通过检测各组患者血清中白介素-10(interleukin-10,IL-10)、IL-17、肿瘤坏死因子-(tumor necrosis factor-β,TNF-β、TGF-β及外周血中调节性T细胞分泌TGF-的水平来分析细胞因子在肝细胞癌转移中作用.结果:通过酶联免疫实验(ELISA)发现发生转移的肝癌患者血清中TNF-TGF-水平明显升高,跟健康对照组比较,差异有统计学意义(P<0.05);同时发现发生转移的肝癌患者血清中TGF-水平与未转移的肝癌患者比较差异也具有统计学意义(P<0.05).通过实时定量PCR以及流式细胞仪进一步确认发生转移的肝癌患者血清中高水平TGF-β主要来源于外周调节性T细胞.结论:TGF-β在肿瘤发生、发展中具有双重作用:在肿瘤发生的起始阶段TGF-扮演着肿瘤抑制者的角色,而在进展期TGF-起着促使肿瘤细胞浸润转移的作用,本研究通过检测外周血中调节性T细胞分泌的TGF-β水平发现只有在发生转移的肝癌患者体内明显升高,可为肝细胞癌转移的筛选与诊断提供指导信息.AIM： To investigate the role of transforming growth factor-b （TGF-b） derived from regulatory T cells in metastasis of hepatocellular carcinoma. METHODS： Forty-eight primary liver cancer patients without metastasis, 32 liver cancer patients with distant metastasis （17 cases of lung metastasis and 15 cases of brain metastasis）, and 54 healthy subjects were included in this study. Serum concentrations of interleukin-10 （IL-10）, IL-17A, tumor necrosis factor-α （TNF-α） and TGF-b were measured by ELISA. Levels of TGF-b in peripheral blood mononuclear cells （PBMCs） and regulatory T cells were determined by flow cytometry and RT-PCR, respectively. RESULTS： Serum levels of TNF-α and TGF-b were significantly increased in liver cancer patients with metastasis compared with normal controls. Serum level of TGF-b was significantly higher in liver cancer patients with metastasis than in liver cancer without metastasis and normal controls （both P 〈 0.05）. Furthermore, we confirmed that TGF-β in liver cancer patients with metastasis was derived from regulatory T cells by quantitative real-time PCR and flow cytometry. CONCLUSION： TGF-b has a dual role in tumorigenesis; it acts as a tumor suppressor in early stage but promotes tumor cell invasion and metastasis in advanced stage. High level of TGF-b was found only in liver cancer patients with metastasis.

关 键 词：肝细胞癌 转化生长因子-Β 调节性T细胞 

分 类 号：R735.7[医药卫生—肿瘤]