S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Presence of Membrane-Bound TGF-β1 and Its Regulation by IL-2-Activated Immune Cell-Derived IFN-γ in Head and Neck Squamous Cell Carcinoma Cell Lines
- Ahn, Yong-Oon; Lee, June-Chul; Sung, Myung-Whun; Heo, Dae Seog
- Issue Date
- AMER ASSOC IMMUNOLOGISTS
- JOURNAL OF IMMUNOLOGY; Vol.182 10; 6114-6120
- The presence of membrane-bound TGF-beta 1 (mTGF-beta 1) has been recently observed in regulatory T cells, but only a few studies have reported the same phenomenon in cancer cells. In this study, we investigate the regulation of mTGF-beta l expression in five head and neck squamous cell carcinoma cell lines using FACS analysis. Through blocking Ab and exogenous cytokine treatment experiments, we found that expression of mTGF-beta 1 is significantly induced by the activated immune cell-derived factor IFN-gamma. In addition, IFN-gamma and TNF-alpha are shown to have a synergistic effect on mTGF-beta 1 expression. Moreover, we found that exogenous TNF-alpha induces endogenous TNF-alpha mRNA expression in an autocrine loop. In contrast to previous reports, we confirm that, in this model, mTGF-beta 1 is neither a rebound form of once-secreted TGF-beta 1 nor an activated form of its precursor membrane latency-associated peptide. Inhibitors of transcription (actinomycin D), translation (cycloheximide), or membrane translocation (brefeldin A) effectively block the induction of mTGF-beta 1, which suggests that induction of mTGF-beta 1 by IFN-gamma and/or TNF-alpha occurs through de novo synthesis. These findings suggest that some cancer cells can detect immune activating cytokines, such as IFN-gamma and TNF-alpha, and actively block antitumor immunity by induction of mTGF-beta 1. The Journal of Immunology, 2009, 182: 6114-6120.
- Files in This Item: There are no files associated with this item.