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
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Atkinson, J. M.
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机构:Univ Bradford, Inst Canc Tehrapeut, Bradford BD7 1DP, W Yorkshire, England
Atkinson, J. M.
Pennington, C. J.
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机构:Univ Bradford, Inst Canc Tehrapeut, Bradford BD7 1DP, W Yorkshire, England
Pennington, C. J.
Martin, S. W.
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Martin, S. W.
Anikin, V. A.
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Anikin, V. A.
Mearns, A. J.
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Mearns, A. J.
Loadman, P. M.
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Loadman, P. M.
Edwards, D. R.
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Edwards, D. R.
Gill, J. H.
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Gill, J. H.
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[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
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.