Presence of membrane-bound TGF-beta1 and its regulation by IL-2-activated immune cell-derived IFN-gamma in head and neck squamous cell carcinoma cell lines.

Abstract

The presence of membrane-bound TGF-beta1 (mTGF-beta1) 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-beta1 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-beta1 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-beta1 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-beta1 is neither a rebound form of once-secreted TGF-beta1 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-beta1, which suggests that induction of mTGF-beta1 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-beta1.

• Authors: Yong-Oon Ahn, June-Chul Lee, Myung-Whun Sung, Dae Seog Heo
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 10 Pg. 6114-20 (May 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19414763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned
• Interleukin-2
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Carcinoma, Squamous Cell (immunology, metabolism)
• Cell Line, Tumor
• Coculture Techniques
• Culture Media, Conditioned
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Gene Expression (immunology)
• Gene Expression Regulation, Neoplastic (immunology)
• Head and Neck Neoplasms (immunology, metabolism)
• Humans
• Interferon-gamma (immunology, metabolism)
• Interleukin-2 (immunology, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta1 (immunology, metabolism)
• Tumor Necrosis Factor-alpha (immunology, metabolism)