The present study was aimed at evaluating the effect of the
matrix metalloproteinase (
MMP) inhibitor prinomastat (
AG3340) on
tumor progression using an orthotopic
pancreatic carcinoma model in severe combined immunodeficient mice. In controls, receiving vehicle only, the poorly differentiated ductal
adenocarcinoma invaded into adjacent organs and metastasized to different sites in the abdomen and to the lungs. Treatment with
prinomastat, intraperitoneally twice daily for 21 days, reduced primary
tumor volume significantly to 19.0 (+/-7.7)% of control, with induction of
necrosis, differentiation, and fibrotic tissue in the pancreatic
tumors. Invasion was not observed in 63% of
prinomastat-treated mice, and
metastases were reduced markedly. Surprisingly,
prinomastat-treated
tumors had on average higher microvessel densities as a consequence of an increased angiogenesis in perinecrotic
tumor areas. We conclude that
prinomastat is highly effective in inhibiting
pancreatic carcinoma growth and progression in an orthotopic
cancer model. This model appears to be a valuable tool to investigate the potency of novel antimetastatic strategies in pancreatic ductal
adenocarcinoma by specifically targeting certain
MMPs.