title: MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas.
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.
authors.affiliation: Cancer Research UK Laboratories, Tom Connors Cancer Research Centre, University of Bradford, Bradford BD7 1DP, UK. j.gill1@bradford.ac.uk
authors.forename: Jason H
authors.initials: JH
authors.lastname: Gill
authors.forename: Ian G
authors.initials: IG
authors.lastname: Kirwan
authors.forename: Jill M
authors.initials: JM
authors.lastname: Seargent
authors.forename: Sandie W
authors.initials: SW
authors.lastname: Martin
authors.forename: Sidiq
authors.initials: S
authors.lastname: Tijani
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Anikin
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mearns
authors.forename: Michael C
authors.initials: MC
authors.lastname: Bibby
authors.forename: Alan
authors.initials: A
authors.lastname: Anthoney
authors.forename: Paul M
authors.initials: PM
authors.lastname: Loadman
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10
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