Matrix metalloproteinases and their clinical relevance in urinary bladder cancer

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.