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

Gill, Jason H.
; 
Kirwan, Ian G.
; 
Seargent, Jill M.
; 
Martin, Sandie W.
; 
Tijani, S.
; 
Anikin, V.A.
; 
Mearns, A.J.
; 
Bibby, Michael C.
; 
Anthoney, Alan
; 
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Publication Date
2004
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Keywords
Tumour Markers, Heterologous, Transplantation, Animals, Carcinoma, Cell line, Tumour, Enzyme activation, Immunohistochemistry, Lung neoplasms, Humans, Matrix Metalloproteinase 10, Metalloendopeptidases, Mice, Biological analysis
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Abstract
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.
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http://hdl.handle.net/10454/4121
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Gill JH, Kirwan IG, Seargent JM et al (2004) MMP-10 is overexpressed, proteolytically active and a potential target for therapeutic intervention in human lung carcinomas. Neoplasia. 6(6): 777-785.
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https://doi.org/10.1593/neo.04283
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