MMP-10 Is Overexpressed, Proteolytically Active, and a Potential Target for Therapeutic Intervention in Human Lung Carcinomas

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2004-11, Vol.6 (6), p.777-785
• Main Authors: Gill, Jason H., Kirwan, Ian G., Seargent, Jill M., Martin, Sandie W., Tijani, Sidiq, Anikin, Vladimir A., Mearns, Alan J., Bibby, Michael C., Anthoney, Alan, Loadman, Paul M.
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers, Tumor - analysis; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Enzyme Activation - physiology; Humans; Immunohistochemistry; Lung Neoplasms - enzymology; Lung Neoplasms - pathology; Matrix metalloproteinase; Matrix Metalloproteinase 10; Metalloendopeptidases - metabolism; Mice; MMP-10; molecular target; non small cell lung carcinoma; Transplantation, Heterologous; tumor development
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1593/neo.04283

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.