HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ahn, Y.-O. Articles by Heo, D. S. Search for Related Content PubMed PubMed Citation Articles by Ahn, Y.-O. Articles by Heo, D. S.

Presence of Membrane-Bound TGF-β1 and Its Regulation by IL-2-Activated Immune Cell-Derived IFN- in Head and Neck Squamous Cell Carcinoma Cell Lines¹

Yong-Oon Ahn^*,, June-Chul Lee^*, Myung-Whun Sung^*, and Dae Seog Heo^2,*,,

^* Cancer Research Institute, Department of Otolaryngology, Department of Internal Medicine, and Innovative Research Institute for Cell Therapy, Seoul National University College of Medicine and Hospital, Seoul, Korea

The presence of membrane-bound TGF-β1 (mTGF-β1) 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-β1 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-β1 is significantly induced by the activated immune cell-derived factor IFN-. In addition, IFN- and TNF- are shown to have a synergistic effect on mTGF-β1 expression. Moreover, we found that exogenous TNF- induces endogenous TNF- mRNA expression in an autocrine loop. In contrast to previous reports, we confirm that, in this model, mTGF-β1 is neither a rebound form of once-secreted TGF-β1 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-β1, which suggests that induction of mTGF-β1 by IFN- and/or TNF- occurs through de novo synthesis. These findings suggest that some cancer cells can detect immune activating cytokines, such as IFN- and TNF-, and actively block antitumor immunity by induction of mTGF-β1.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by grants from the Innovative Research Institute for Cell Therapy (A062260) and the Korea Health 21 Research & Development Project (02-PJ1-PG3-21206-0003), Ministry of Health and Welfare, Republic of Korea.

² Address correspondence and reprint requests to Dr. Dae Seog Heo, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea, E-mail address: heo1013{at}snu.ac.kr

³ Abbreviations used in this paper: Treg, regulatory T cell; HNSCC, head and neck squamous cell carcinoma; mTGF-β1, membrane-bound TGF-β1; CM, conditioned medium; LAP, latency-associated peptide; ActD, actinomycin D; CHX, cycloheximide; BFA, brefeldin A; rh, recombinant human.