Matrix metalloproteinase inhibitors (MMPI) and their therapeutic application for GI tract cancer

The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound zinc-endopeptidases. These enzymes are capable of degrading components of the extracellular matrix including collagens, laminin, proteoglycan, fibronectin, and others. In some human GI tract cancers, a positive correlation has been demonstrated between MMP expression and the likelihood of developing metastasis. Numerous reports concerning the role of MMPs during cancer invasion and metastasis have been published. Based on this, inhibition of MMPS has in recent years been recognized as a therapeutic target of particular interest. In order to evaluate the therapeutic effects of MMPI, we have established a nude mouse peritoneal dissemination model. Two MMPIs, matlystatin and marimastat, have been found to inhibit peritoneal dissemination formation. Recent advances in MMP research and reports on the clinical application of MMPIs are reviewed in this paper.