TGF-β Regulates Hepatocellular Carcinoma Progression by Inducing Treg Cell Polarization
| Autor: | Rong Li, Zhouchong Wang, Yi-Nan Shen, Yingying Jing, Haiguan He, Yongpeng Wei, Tian Yang, Jianyong Yuan, Jun-Hua Lu, Qiu-dong Zhao, Lixin Wei |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Carcinoma Hepatocellular Physiology Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena T-Lymphocytes Regulatory lcsh:Physiology lcsh:Biochemistry Mice Transforming Growth Factor beta Carcinoma medicine Animals lcsh:QD415-436 Diethylnitrosamine HCC Receptor neoplasms Cell Proliferation TGF-β lcsh:QP1-981 business.industry Liver Neoplasms Cell Polarity Membrane Proteins FOXP3 Cell Differentiation Forkhead Transcription Factors hemic and immune systems Phosphoproteins medicine.disease digestive system diseases In vitro Interleukin-10 Up-Regulation Disease Models Animal Interleukin 10 Hepatocellular carcinoma Immunology Disease Progression Immunohistochemistry business Azabicyclo Compounds Receptors Transforming Growth Factor beta Treg cells Transforming growth factor |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 35, Iss 4, Pp 1623-1632 (2015) |
| ISSN: | 1421-9778 1015-8987 |
| DOI: | 10.1159/000373976 |
| Popis: | 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. 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. Conclusion: TGF-β is necessary for HCC progression, acting by inducing Treg cell polarization. |
| Databáze: | OpenAIRE |
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