Matrix metalloproteinases (
MMPs), and especially membrane type-1
matrix metalloproteinase (MT1-MMP, MMP-14), play a role in
cancer progression and can have a prognostic value. Various synthetic broad-spectrum
MMP inhibitors have been developed but have had little success in
cancer patient treatment owing to side effects. Until recently, selective targeting of specific
MMPs has not been possible due to lack of specific inhibitors. Here we have developed a selective
MT1-MMP peptide-inhibitor GACFSIAHECGA, which did not affect the activities of many other
MMPs including MMP-1, -2, -3, -7, -8, -9, -10, -11, -12, -13, -15, -17 or -20. In a fluorescent
peptide cleavage assay it displayed an IC(50) value of 150 microM. The
peptide effectively inhibited the migration and invasion of
cancer cell lines in vitro. Furthermore, in vivo the
peptide reduced the growth of tongue
carcinoma xenografts and prolonged the survival of mice. Overall these results suggest that selective
MT1-MMP inhibitors may have utility as
anticancer agents.