Matrix metalloproteinases in colorectal cancer

Matrix metalloproteinases (MMPs) appear to play a key role in the development and progression of human malignancies. MMPs mediate the destruction of the extracellular matrix, which is an important early step in tumor invasion and metastasis. Growing evidence suggests that MMPs also have angiogenic activity and participate in the early stages of tumorigenesis and primary tumor growth. Investigations in experimental animal models have confirmed the importance of MMPs in the pathogenesis of colorectal cancer, and studies in humans show a direct association between increased MMP expression and tumor invasiveness, development of metastases, and shortened survival. In this review, the physiologic role of MMPs in normal tissues is examined and data supporting the role of MMPs in the pathogenesis of colorectal cancer are reviewed. The results of clinical trials with MMP inhibitors in colorectal cancer and promising areas for future investigation are also discussed.