Matrix metalloproteinases and their clinical relevance in urinary bladder cancer

• Published in: Nature reviews. Urology Vol. 8; no. 5; pp. 241 - 254
• Main Authors: Szarvas, Tibor, vom Dorp, Frank, Ergün, Süleyman, Rübben, Herbert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2011; Nature Publishing Group
• Subjects: 692/420/755; 692/53/2421; 692/699/67/589/1336; Animals; Bladder cancer; Diagnosis; Extracellular Matrix - drug effects; Extracellular Matrix - enzymology; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - metabolism; Medicine; Medicine & Public Health; Physiological aspects; Protease Inhibitors - pharmacology; Proteases; review-article; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - enzymology; Urology; Germany
• ISSN: 1759-4812; 1759-4820; 1759-4820
• DOI: 10.1038/nrurol.2011.44

Matrix metalloproteinases (MMPs) are a family of enzymes that have a number of important functions, including regulation of the extracellular matrix, angiogenesis and apoptosis. MMP dysregulation has been implicated in several disease processes. In this Review, the authors describe the role of MMPs in bladder cancer, and how these enzymes seem to have potential as diagnostic and prognostic biomarkers or as targets for therapy in patients with this disease. Matrix metalloproteinases (MMPs) have important roles in several cancer-supporting cellular processes, such as extracellular matrix (ECM) remodeling, angiogenesis, apoptosis, epithelial-to-mesenchymal transition and cell proliferation. This broad range of activity has led to considerable interest in the use of MMPs in the clinical setting as diagnostic or prognostic biomarkers and as therapeutic targets. Levels of the different MMPs can be measured in several sample types, including paraffin-embedded or fresh frozen tissue, serum, plasma and urine, and by various analytical methodologies, such as immunohistochemistry, real-time PCR, western and northern blot analyses, enzyme-linked immunosorbent assay and zymography. Several MMPs have been identified as having potential diagnostic or prognostic utility, whether alone or in combination with currently available diagnostic tests or imaging modalities. Although the early broad-spectrum anti-MMP agents showed a lack of efficacy, our continually improving understanding of the complex physiologic and pathologic roles of MMPs might enable the development of new MMP-specific and tumor-specific therapies. Accordingly, MMPs will continue to be the subjects of intensive research in bladder cancer. Key Points Matrix metalloproteinases (MMPs) are zinc-dependent endogenous proteases with distinct but partly overlapping substrate specificities and structural similarities The proteolytic activity of MMPs is regulated by transcription factors, endogenous inhibitors, and proteases that are able to remove the pro-domains of MMPs from their inactive, latent form MMPs are involved in several physiological and tumor-supporting cellular processes, including loss of cell adhesion, tumor angiogenesis, cell proliferation, epithelial-to-mesenchymal transition and apoptosis MMP levels can be assessed in various sample types (tissue, serum, plasma and urine) using several methods (immunohistochemistry, real-time PCR, western and northern blot analyses, enzyme-linked immunosorbent assay and zymography) MMPs have been extensively analyzed in bladder cancer, which has revealed potential roles for some MMPs as diagnostic markers and prognostic factors at different stages of the disease course Although broad-spectrum anti-MMP agents provided disappointing results, MMPs remain promising targets for tumor therapy; tissue-specific and/or selective MMP inhibition combined with novel imaging techniques might allow development of effective new anti-MMP therapies