TGF-β Regulates Hepatocellular Carcinoma Progression by Inducing Treg Cell Polarization

Background/Aims: TGF-beta plays a key role in the progression of various tumors. The main objective of our study was to investigate whether TGF-beta is a ble to regulate N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) progression in a mouse model by inducing Treg cell polarization. Methods: HCC progression, TGF-p and Foxp3 expression levels, serum TGF-beta, 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-beta on Treg cell polarization in vitro was measured by flow cytometric analysis. The expression of TGF-beta and IL10 was identified by IHC in HCC patients and the correlation between TGF-beta and IL10 was also assessed. Results: TGF-beta expression is up-regulated in a DEN-induced HCC mouse model. TGF-beta can promote the differentiation of Foxp3(+)CD4(+) T cells (Treg cells) in vitro. However, blocking the TGF-beta pathway with a specific TGF-beta receptor inhibitor, SM-16, reduced HCC progression and the percentage of Treg cells in liver tissue. The correlation between TGF-beta and Treg cells was also confirmed in HCC patients and the expression of both TGF-beta and IL-10 was shown to be associated with HCC progression. Conclusion: TGF-beta is necessary for HCC progression, acting by inducing Treg cell polarization. Copyright (C) 2015 S. Karger AG, Basel