Role of matrix metalloproteinases in invasion and metastasis: biology, diagnosis and inhibitors.

The processes of tumour invasion and subsequent metastasis are the most lethal aspects of cancer. Whilst many factors are involved, the matrix metalloproteinases (MMPs) have been implicated as key-rate limiting enzymes in the invasive process. This family consisting of eight members of similar structure, can be roughly divided into three groups based on substrate specificity. All are secreted in a latent form and require proteolytic cleavage for activation. The expression of these enzymes is regulated at the transcriptional level by a variety of growth factors and oncogenes. They are also regulated at the protein level by a family of specific inhibitors called the tissue inhibitors of metalloproteinases (TIMPs). Studies in human tumour samples have shown a positive correlation between metalloproteinase expression and metastatic potential. The levels of metalloproteinase expression have been manipulated using molecular biology techniques in several cell lines and shown a similar correlation. These results suggest that an understanding of metalloproteinase expression and proteolytic activity may lead to the development of effective therapeutic agents with the potential to reduce the incidence of metastatic cancer.