Membrane type matrix metalloproteinases (MMPs) show differential expression in non-small cell lung cancer (NSCLC) compared to normal lung: Correlation of MMP-14 mRNA expression and proteolytic activity

被引:39
作者
Atkinson, J. M.
Pennington, C. J.
Martin, S. W.
Anikin, V. A.
Mearns, A. J.
Loadman, P. M.
Edwards, D. R.
Gill, J. H.
机构
[1] Univ Bradford, Inst Canc Tehrapeut, Bradford BD7 1DP, W Yorkshire, England
[2] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England
[3] Bradford Royal Infirm, Dept Cardiothorac Surg, Bradford BD9 6RJ, W Yorkshire, England
基金
英国医学研究理事会;
关键词
matrix metalloproteinases; membrane-type metalloproteinases; lung cancer; real-time PCR; carcinoma; non-small cell lung; cancer therapeutics; GELATINASE-A; MT-MMPS; INHIBITORS; CARCINOMAS; MIGRATION; IDENTIFICATION; ANGIOGENESIS; DEGRADOMICS; PROGRESSION; MT1-MMP;
D O I
10.1016/j.ejca.2007.05.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Improved understanding of the involvement of matrix metalloproteinases (MMPs), including membrane-type MMPs (MT-MMPs), in human tumours has potential diagnostic, prognostic and therapeutic implications. We assessed the relationship between MT-MMP expression and clinicopathological parameters in human non-small cell lung cancer (NSCLC) and histologically normal lung tissue by quantitative Real Time PCR (qRT-PCR). All MT-MMPs (MMPs 14-17, 24 and 25) were detected by qRT-PCR with significantly higher MMP-14, -15 and -17 expression observed in tumour relative to normal lung specimens. MMP-16 was undetectable in normal lung but expressed in 8% turnours. MMP-15 demonstrated significant overexpression in adenocarcinomas relative to squamous cell carcinomas and normal lung tissue. MMP-14 mR.NA expression strongly correlated to MMP-14 proteolytic activity in preclinical tumour models, indicating that qRT-PCR may predict MMP-14 activity levels in NSCLC. These data suggest that MMP-14, -15 and -17 may be good markers of disease, or therapeutic targets for treatment of human NSCLC. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1764 / 1771
页数:8
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