Significance of the TGF-β I/IL-6 axis in oral cancer

被引：38
作者：
Chen, Miao-Fen [1 ,2 ]
Wang, Wen-Hung [2 ,3 ]
Lin, Paul-Yang [4 ]
Lee, Kuan-Der [2 ,5 ]
Chen, Wen-Cheng [1 ,2 ]
机构：
[1] Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan
[2] Chang Gung Univ, Coll Med, Tao Yuan, Taiwan
[3] Chang Gung Mem Hosp, Dept Otolaryngol Head & Neck Surg, Chiayi, Taiwan
[4] Chang Gung Mem Hosp, Dept Pathol, Chiayi, Taiwan
[5] Chang Gung Mem Hosp, Dept Hematol & Oncol, Chiayi, Taiwan
来源：
CLINICAL SCIENCE | 2012年 / 122卷 / 9-10期
关键词：
epithelial-mesenchymal transition; head and neck squamous cell carcinoma; interleukin-6 (IL-6); oral cancer; transforming growth factor-beta 1 (TGF-beta 1); SQUAMOUS-CELL CARCINOMA; NECK-CANCER; HEAD; PROGRESSION; PATHWAYS; PHOSPHORYLATION; CHEMOTHERAPY; INFLAMMATION; IRRADIATION; INVOLVEMENT;
D O I：
10.1042/CS20110434
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
The aim of the present study was to explore specific molecular markers that could lead to new insights into the identification of innovative treatments in oral cancer. The role of TGF-beta 1 (transforming growth factor-beta 1) and its predictive power in the prognosis of oral cancer has been identified. Human oral cancer cell lines, including SCC4 and SCC25, were selected for cellular experiments. Changes in tumour aggressiveness, responses to treatment and the signalling pathway responsible were investigated in vitro. Furthermore, 125 oral cancer tissue specimens were constructed into tissue microarray blocks for immunohistochemical analysis to correlate the expression of TGF-beta 1 with clinical outcome. Using in vitro experiments, our results revealed that activated TGF-beta 1 signalling resulted in more aggressive tumour growth, augmented the epithelial-mesenchymal transition and more resistance to treatment. Activated IL-6 (interleukin-6) signalling could be the mechanism underlying the effects of TGF-beta 1 on oral cancer. Regarding clinical data, the incidence of TGF-beta 1 immunoreactivity in oral cancer specimens was significantly higher than in non-malignant epithelium and positively linked to IL-6 staining. Furthermore, expression of TGF-beta 1 was significantly correlated with the risk of lymph node involvement, disease recurrence and shorter survival in patients with pathological stage III-IV oral cancer. In conclusion, the TGF-alpha beta I/IL-6 axis had predictive power in the prognosis of oral cancer, and targeting TGF-beta 1 could represent a promising treatment strategy.
引用
收藏
页码：459 / 472
页数：14
相关论文
共 25 条
[1]   Head and neck cancer [J].
Argiris, Athanassios ;
Karamouzis, Michalis V. ;
Raben, David ;
Ferris, Robert L. .
LANCET, 2008, 371 (9625) :1695-1709
[2]   Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer [J].
Bernier, J ;
Domenge, C ;
Ozsahin, M ;
Matuszewska, K ;
Lefèbvre, JL ;
Greiner, RH ;
Giralt, J ;
Maingon, P ;
Rolland, F ;
Bolla, M ;
Cognetti, F ;
Bourhis, J ;
Kirkpatrick, A ;
van Glabbeke, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (19) :1945-1952
[3]   Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation [J].
Bornstein, Sophia ;
White, Ruth ;
Malkoski, Stephen ;
Oka, Masako ;
Han, Gangwen ;
Cleaver, Timothy ;
Reh, Douglas ;
Andersen, Peter ;
Gross, Neil ;
Olson, Susan ;
Deng, Chuxia ;
Lu, Shi-Long ;
Wang, Xiao-Jing .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (11) :3408-3419
[4]   SIGNIFICANCE OF INTERLEUKIN-6 SIGNALING IN THE RESISTANCE OF PHARYNGEAL CANCER TO IRRADIATION AND THE EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITOR [J].
Chen, Chih-Cheng ;
Chen, Wen-Cheng ;
Lu, Chang-Hsien ;
Wang, Wen-Hung ;
Lin, Paul-Yang ;
Lee, Kuan-Der ;
Chen, Miao-Fen .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2010, 76 (04) :1214-1224
[5]   Sustained TGFβ exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis [J].
Gal, A. ;
Sjoeblom, T. ;
Fedorova, L. ;
Imreh, S. ;
Beug, H. ;
Moustakas, A. .
ONCOGENE, 2008, 27 (09) :1218-1230
[6]  
HU L, 1991, CANCER RES, V51, P3972
[7]   Predictive Value of Tumor Thickness for Cervical Lymph-Node Involvement in Squamous Cell Carcinoma of the Oral Cavity A Meta-analysis of Reported Studies [J].
Huang, Shao Hui ;
Hwang, David ;
Lockwood, Gina ;
Goldstein, David P. ;
O'Sullivan, Brian .
CANCER, 2009, 115 (07) :1489-1497
[8]   The many substrates and functions of ATM [J].
Kastan, MB ;
Lim, DS .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2000, 1 (03) :179-186
[9]   Inhibition of transforming growth factor-β1 signaling attenuates ataxia telanglectasia mutated activity in response to genotoxic stress [J].
Kirshner, Julia ;
Jobling, Michael F. ;
Pajares, Maria Jose ;
Ravani, Shraddha A. ;
Glick, Adam B. ;
Lavin, Martin J. ;
Koslov, Sergei ;
Shiloh, Yosef ;
Barcellos-Hoff, Mary Helen .
CANCER RESEARCH, 2006, 66 (22) :10861-+
[10]   Alterations in components of the TGF-β superfamily signaling pathways in human cancer [J].
Levy, L ;
Hill, CS .
CYTOKINE & GROWTH FACTOR REVIEWS, 2006, 17 (1-2) :41-58
123