ROLE OF MATRIX METALLOPROTEINASES IN INVASION AND METASTASIS - BIOLOGY, DIAGNOSIS AND INHIBITORS

The processes of tumour invasion and subsequent metastasis are the mos t lethal aspects of cancer. Whilst many factors are involved, the matr ix metalloproteinases (MMPs) have been implicated as key-rate limiting enzymes in the invasive process. This family consisting of eight memb ers of similar structure, can be roughly divided into three groups bas ed on substrate specificity. All are secreted in a latent form and req uire proteolytic cleavage for activation. The expression of these enzy mes is regulated at the transcriptional level by a variety of growth f actors and oncogenes. They are also regulated at the protein level by a family of specific inhibitors called the tissue inhibitors of metall oproteinases (TIMPs). Studies in human tumour samples have shown a pos itive correlation between metalloproteinase expression and metastatic potential. The levels of metalloproteinase expression have been manipu lated using molecular biology techniques in several cell lines and sho wn a similar correlation. These results suggest that an understanding of metalloproteinase expression and proteolytic activity may lead to t he development of effective therapeutic agents with the potential to r educe the incidence of metastatic cancer.