期刊
BRITISH JOURNAL OF CANCER
卷 104, 期 1, 页码 138-145出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6606017
关键词
TACE; TIMP3; squamous cell carcinoma of the head and neck (HNSCC)
类别
资金
- Deutsche Krebshilfe [70-2922]
BACKGROUND: TACE/ADAM17 is a transmembranous protease that cleaves membrane-bound growth factors like EGFR ligands. TACE-dependent proteolysis is regulated by its inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP3). This study analyses the role of TACE and TIMP3 mRNA expression in squamous cell carcinomas of the head and neck (HNSCCs). METHODS: We analysed TACE and TIMP3 mRNA expression in HNSCCs from 106 patients by RNA in situ hybridisation. RESULTS: TACE mRNA was upregulated in HNSCCs compared with dysplastic (P<0.05) and normal epithelia (P<0.001), with strong hybridisation signals in 21.9% of invasive tumour tissues and 4.5% of dysplasia. Elevated mRNA levels were accompanied by increased amounts of TACE protein in HNSCCs. TIMP3 mRNA expression in HNSCC-associated stroma was significantly higher than in the stroma adjacent to dysplastic or normal epithelia. Expression of TACE mRNA in HNSCCs was associated with tumour stage (P = 0.019) and regional lymph node metastasis (P = 0.009). Furthermore, levels of TACE mRNA in HNSCCs correlated with the expression of TIMP3 mRNA in HNSCC-associated stroma. Concomitantly, patients expressing high levels of TACE and TIMP3 mRNA showed significantly reduced overall survival compared with those with low mRNA levels. CONCLUSION: Our results indicate an important role of TACE and TIMP3 during development and progression of HNSCCs. British Journal of Cancer (2011) 104, 138-145. doi:10.1038/sj.bjc.6606017 www.bjcancer.com Published online 23 November 2010 (C) 2011 Cancer Research UK
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