Dipeptidyl peptidase IV (DPPIV) and seprase, Mr 170,000 - 200,000 surface-bound serine, prolyl dipeptidases; comprising of homodimers; sharing similar structural and proteolytic activities with each other, are absent in normal endothelia and stroma but together they have a role in the development of invasive phenotypes of various cells in certain human cancers. A specific DPPIV form is co-expressed with seprase in various tumor cell lines, as well as cells activated for cancer invasion in vivo, including carcinoma, stromal and angiogenic endothelial cells in invasive carcinoma of the breast. For example, the DPPIV-seprase association was found in the endothelial cells that were active in migration, sprouting and invasion into ECM gels from monolayer and in angiogenesis models in vitro. In contrast, ß1 integrins, MT1-MMP and MMP-2 are constitutively expressed in all endothelial cells. Antibodies specific for the DPPIV form blocked endothelial migration, sprouting and ECM gel-invasion but did not affect preexisting capillaries; whereas ß1 antibodies or MMP inhibitors strongly disturbed both processes. Because the DPPIV form associated with seprase is present at very low levels in differentiated endothelium, it makes attractive new therapeutic targets for cancer invasion and angiogenesis.
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