title: 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.
abstract: 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% tumours. MMP-15 demonstrated significant overexpression in adenocarcinomas relative to squamous cell carcinomas and normal lung tissue. MMP-14 mRNA 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.
authors.affiliation: Institute of Cancer Therapeutics, University of Bradford, Tumbling Hill Street, Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Atkinson
authors.forename: C J
authors.initials: CJ
authors.lastname: Pennington
authors.forename: S W
authors.initials: SW
authors.lastname: Martin
authors.forename: V A
authors.initials: VA
authors.lastname: Anikin
authors.forename: A J
authors.initials: AJ
authors.lastname: Mearns
authors.forename: P M
authors.initials: PM
authors.lastname: Loadman
authors.forename: D R
authors.initials: DR
authors.lastname: Edwards
authors.forename: J H
authors.initials: JH
authors.lastname: Gill
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020782:Matrix Metalloproteinases; D053511:Matrix Metalloproteinase 14