Atkinson J M, Pennington C J, Martin S W, Anikin V A, Mearns A J, Loadman P M, Edwards D R, Gill J H
Institute of Cancer Therapeutics, University of Bradford, Tumbling Hill Street, Bradford, West Yorkshire, BD7 1DP, UK.
Eur J Cancer. 2007 Jul;43(11):1764-71. doi: 10.1016/j.ejca.2007.05.009. Epub 2007 Jun 27.
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.
对包括膜型基质金属蛋白酶（MT - MMPs）在内的基质金属蛋白酶（MMPs）在人类肿瘤中的作用有更深入的了解，具有潜在的诊断、预后和治疗意义。我们通过定量实时聚合酶链反应（qRT - PCR）评估了MT - MMP表达与人类非小细胞肺癌（NSCLC）及组织学正常肺组织中临床病理参数之间的关系。通过qRT - PCR检测到所有MT - MMPs（MMPs 14 - 17、24和25），相对于正常肺标本，在肿瘤中观察到MMP - 14、- 15和- 17表达显著更高。MMP - 16在正常肺中未检测到，但在8%的肿瘤中表达。相对于鳞状细胞癌和正常肺组织，MMP - 15在腺癌中表现出显著过表达。在临床前肿瘤模型中，MMP - 14 mRNA表达与MMP - 14蛋白水解活性强烈相关，表明qRT - PCR可预测NSCLC中MMP - 14活性水平。这些数据表明，MMP - 14、- 15和- 17可能是疾病的良好标志物，或为人类NSCLC治疗的治疗靶点。
