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MMP-10 is overexpressed, proteolytically active and a potential target for therapeutic intervention in human lung carcinomas

No / Matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix is a major factor for tumor development and expansion. This study analysed MMP-10 protein expression and activity in human lung tumors of various grade, stage, and type to address the relationship between MMP-10 and tumor characteristics and to evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC). Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to tumor stroma. MMP-10 protein was observed at low levels in normal human lung tissues and at significantly higher levels in all types of NSCLC. No correlation was observed between MMP-10 protein expression and tumor type, stage, or lymph node invasion. To discriminate between active and inactive forms of MMP-10 in samples of human NSCLC, we have developed an ex vivo fluorescent assay. Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and only 2 of 10 specimens of histologically normal lung tissue. No relationship was observed between MMP-10 activity levels and clinicopathologic characteristics. Our results suggest that MMP-10 is expressed and active at high levels in human NSCLC compared to normal lung tissues, and, as such, is a potential target for the development of novel therapeutics for lung cancer treatment.

Identiferoai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/4121
Date January 2004
CreatorsGill, Jason H., Kirwan, Ian G., Seargent, Jill M., Martin, Sandie W., Tijani, S., Anikin, V.A., Mearns, A.J., Bibby, Michael C., Anthoney, Alan, Loadman, Paul
Source SetsBradford Scholars
LanguageEnglish
Detected LanguageEnglish
TypeArticle, No full-text in the repository

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