Matrix metalloproteinases in tumour invasion and metastasis

Abstract

The matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. The MMPs have been classified into different groups including collagenases, gelatinases, stromelysins, and others, particularly membrane-type MMPs, based mainly on the in vitro substrate specificity of individual MMPs. There is increasing evidence to indicate that individual MMPs have important roles in tumour invasion and metastasis. However, the current concept of the role of MMPs in tumour invasion is that they not only have a direct role in tumour invasion by facilitating extracellular matrix degradation, but as a consequence they also have an important role in maintaining the tumour micro-environment and thus promoting tumour growth. Inhibiting the action of MMPs represents a new therapeutic approach for the treatment of individual types of cancer and several broad-spectrum, low-molecular-weight MMP inhibitors are currently being assessed for clinical use. This review examines the role of MMPs in tumour invasion and metastasis, with an emphasis on studies of clinical relevance.