Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

• Published in: British journal of cancer Vol. 94; no. 4; pp. 569 - 577
• Main Authors: WALLARD, M. J, PENNINGTON, C. J, KELLY, J. I. D, VEERAKUMARASIVAM, A, BURTT, G, MILLS, I. G, WARREN, A, LEUNG, H. Y, MURPHY, G, EDWARDS, D. R, NEAL, D. E
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 27.02.2006
• Subjects: Biological and medical sciences; Biomarkers, Tumor - analysis; Bladder cancer; Cancer research; Extracellular matrix; Gene Expression Profiling; Humans; Localization; Matrix Metalloproteinases - analysis; Matrix Metalloproteinases - biosynthesis; Matrix Metalloproteinases - metabolism; Medical research; Medical sciences; Metastasis; Molecular Diagnostics; Physiology; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Tissue Distribution; Tumors; Urinary Bladder Neoplasms - enzymology; Urinary Bladder Neoplasms - pathology; United Kingdom > UK; RNA-directed DNA polymerase; Microdissection; Enzyme; Transferases; Metalloendopeptidases; urothelial cancer; Transitional cell carcinoma; Malignant tumor; laser capture microdissection; Capture; Peptidases; MMP; Nucleotidyltransferases; Cancerology; Laser; quantitative RT-PCR; Hydrolases; Molecular biology; Reverse transcription polymerase chain reaction; Quantitative analysis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602931

The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT-PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (P < 0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer.