PMID- 15720804 OWN - NLM STAT- MEDLINE DCOM- 20050421 LR - 20181113 IS - 1522-8002 (Print) IS - 1476-5586 (Electronic) IS - 1476-5586 (Linking) VI - 6 IP - 6 DP - 2004 Nov-Dec TI - MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas. PG - 777-85 AB - 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. FAU - Gill, Jason H AU - Gill JH AD - Cancer Research UK Laboratories, Tom Connors Cancer Research Centre, University of Bradford, Bradford BD7 1DP, UK. j.gill1@bradford.ac.uk FAU - Kirwan, Ian G AU - Kirwan IG FAU - Seargent, Jill M AU - Seargent JM FAU - Martin, Sandie W AU - Martin SW FAU - Tijani, Sidiq AU - Tijani S FAU - Anikin, Vladimir A AU - Anikin VA FAU - Mearns, Alan J AU - Mearns AJ FAU - Bibby, Michael C AU - Bibby MC FAU - Anthoney, Alan AU - Anthoney A FAU - Loadman, Paul M AU - Loadman PM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (Biomarkers, Tumor) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.22 (Matrix Metalloproteinase 10) SB - IM MH - Animals MH - Biomarkers, Tumor/analysis MH - Carcinoma, Non-Small-Cell Lung/*enzymology/*pathology MH - Cell Line, Tumor MH - Enzyme Activation/physiology MH - Humans MH - Immunohistochemistry MH - Lung Neoplasms/*enzymology/*pathology MH - Matrix Metalloproteinase 10 MH - Metalloendopeptidases/*metabolism MH - Mice MH - Transplantation, Heterologous PMC - PMC1550316 EDAT- 2005/02/22 09:00 MHDA- 2005/04/22 09:00 PMCR- 2004/11/01 CRDT- 2005/02/22 09:00 PHST- 2005/02/22 09:00 [pubmed] PHST- 2005/04/22 09:00 [medline] PHST- 2005/02/22 09:00 [entrez] PHST- 2004/11/01 00:00 [pmc-release] AID - 04283 [pii] AID - 10.1593/neo.04283 [doi] PST - ppublish SO - Neoplasia. 2004 Nov-Dec;6(6):777-85. doi: 10.1593/neo.04283.