Roles of membrane-type matrix metalloproteinase-1 in tumor invasion and etastasis

Degradation of extracellular matrix (ECM) is one of the first steps in tumor invasion and metastasis. Matrix metalloproteinases (MMP) have been strongly implicated in this step. Membrane-type MMP-1 (MT1-MMP) was first identified as an activator of proMMP-2 expressed on the surface of tumor cells and later, not only ECM macromolecules but also various biologically important molecules, were shown to serve as substrates for MT1-MMP. Accumulated lines of evidence have demonstrated that MT1-MMP expression level is closely associated with invasiveness and malignancy of tumors, suggesting that MT1-MMP is one of the most critical factors for tumor invasion and metastasis. Despite enthusiasm for MMP inhibitors, phase III trials have not yet demonstrated significance in overall survival and side-effects remain an issue. An understanding of the functions of MT1-MMP could supply clues for developing novel therapeutic strategies targeting MT1-MMP.