Shen Yinan, Wei Yongpeng, Wang Zhouchong, Jing Yingying, He Haiguan, Yuan Jianyong, Li Rong, Zhao Qiudong, Wei Lixin, Yang Tian, Lu Junhua
The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
Cell Physiol Biochem. 2015;35(4):1623-32. doi: 10.1159/000373976. Epub 2015 Mar 18.
BACKGROUND/AIMS: TGF-β plays a key role in the progression of various tumors. The main objective of our study was to investigate whether TGF-β is able to regulate N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) progression in a mouse model by inducing Treg cell polarization.
HCC progression, TGF-β and Foxp3 expression levels, serum TGF-β, IL10 and GP73 levels as well as percentage of Treg cells were analyzed in healthy, HCC and HCC+SM-16 mouse groups. The effect of TGF-β on Treg cell polarization in vitro was measured by flow cytometric analysis. The expression of TGF-β and IL10 was identified by IHC in HCC patients and the correlation between TGF-β and IL10 was also assessed.
TGF-β expression is up-regulated in a DEN-induced HCC mouse model. TGF-β can promote the differentiation of Foxp3(+)CD4(+) T cells (Treg cells) in vitro. However, blocking the TGF-β pathway with a specific TGF-β receptor inhibitor, SM-16, reduced HCC progression and the percentage of Treg cells in liver tissue. The correlation between TGF-β and Treg cells was also confirmed in HCC patients and the expression of both TGF-β and IL-10 was shown to be associated with HCC progression.
TGF-β is necessary for HCC progression, acting by inducing Treg cell polarization.
背景/目的：转化生长因子-β（TGF-β）在多种肿瘤进展中起关键作用。我们研究的主要目的是探讨TGF-β是否能够通过诱导调节性T细胞（Treg细胞）极化来调控二乙基亚硝胺（DEN）诱导的小鼠肝细胞癌（HCC）进展。
分析健康、HCC和HCC+SM-16小鼠组中的HCC进展、TGF-β和叉头框蛋白3（Foxp3）表达水平、血清TGF-β、白细胞介素10（IL10）和高尔基体蛋白73（GP73）水平以及Treg细胞百分比。通过流式细胞术分析测定TGF-β对体外Treg细胞极化的影响。通过免疫组化法（IHC）鉴定HCC患者中TGF-β和IL10的表达，并评估TGF-β与IL10之间的相关性。
在DEN诱导的HCC小鼠模型中，TGF-β表达上调。TGF-β在体外可促进Foxp3(+)CD4(+) T细胞（Treg细胞）的分化。然而，用特异性TGF-β受体抑制剂SM-16阻断TGF-β信号通路可降低HCC进展及肝组织中Treg细胞的百分比。在HCC患者中也证实了TGF-β与Treg细胞之间的相关性，并且TGF-β和IL-10的表达均与HCC进展相关。
TGF-β通过诱导Treg细胞极化对HCC进展至关重要。
