title: TGF-β regulates hepatocellular carcinoma progression by inducing Treg cell polarization.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  TGF-β is necessary for HCC progression, acting by inducing Treg cell polarization.
authors.affiliation: The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Shen
authors.forename: Yongpeng
authors.initials: Y
authors.lastname: Wei
authors.forename: Zhouchong
authors.initials: Z
authors.lastname: Wang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Jing
authors.forename: Haiguan
authors.initials: H
authors.lastname: He
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yuan
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Qiudong
authors.initials: Q
authors.lastname: Zhao
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.forename: Junhua
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D053961:Azabicyclo Compounds / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D051379:Mice; D010750:Phosphoproteins / Q000097:blood; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053961:Azabicyclo Compounds; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C546580:Golm1 protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D018125:Receptors, Transforming Growth Factor beta; C528106:SM16 compound; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D004052:Diethylnitrosamine