MMP-7 marks severe pancreatic cancer and alters tumor cell signaling by proteolytic release of ectodomains

Pancreatic cancer incurs the worst survival rate of the major cancers. High levels of the protease matrix metalloproteinase-7 (MMP-7) in circulation correlate with poor prognosis and limited survival of patients. MMP-7 is required for a key path of pancreatic tumorigenesis in mice and is present throughout tumor progression. Enhancements to chemotherapies are needed for increasing the number of pancreatic tumors that can be removed and for preventing relapses after surgery. With these ends in mind, selective inhibition of MMP-7 may be worth investigation. An anti-MMP-7 monoclonal antibody was recently shown to increase the susceptibility of several pancreatic cancer cell lines to chemotherapeutics, increase their apoptosis, and decrease their migration. MMP-7 activities are most apparent at the surfaces of innate immune, epithelial, and tumor cells. Proteolytic shedding of multiple protein ectodomains by MMP-7 from such cell surfaces influence apoptosis, proliferation, migration, and invasion. These activities warrant targeting of MMP-7 selectively in pancreatic cancer and other tumors of mucosal epithelia. Competitive and non-competitive modes of MMP-7 inhibition are discussed.