Dipeptidyl peptidase IV (DPP4/CD26) and seprase / fibroblast activation protein alpha (FAP-α), are homologous type II transmembrane, homodimeric glycoproteins that exhibit unique prolyl peptidase activities. Human DPP4 is ubiquitously expressed in epithelial and endothelial cells and serves multiple functions in cleaving the penultimate positioned prolyl bonds at the N-terminus of a variety of physiologically important peptides in the circulation. Recent studies showed a linkage between DPP4 and down-regulation of certain chemokines and mitogenic growth factors, and degradation of denatured collagens (gelatin), suggesting a role of DPP4 in the cell invasive phenotype. Here, we found the existence of a novel protease complex consisting of DPP4 and seprase in human endothelial cells that were activated to migrate and invade in the ECM in vitro. DPP4 and seprase were co-expressed with the three major protease systems (MMP, PA and TTSP) at the cell surface and organize as a complex at invadopodia-like protrusions. Both proteases were co-localized at the endothelial cells of capillaries but not large blood vessels in invasive breast ductal carcinoma in vivo. Importantly, mAbs against the gelatin-binding domain of DPP4 blocked the local gelatin degradation by endothelial cells in the presence of the major metallo- and serine-protease systems that modified peri-cellular collagenous matrices, and subsequent cell migration and invasion. Thus, we have identified a novel mechanism involving the DPP4 gelatin-binding domain of the DPP4-seprase complex that facilitates the local degradation of the ECM and the invasion of the endothelial cells into collagenous matrices.
|Data di pubblicazione:||2006|
|Titolo:||The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices.|
|Autori:||GHERSI, G; ZHAO, Q; SALAMONE, M; YEH, Y; ZUCKER, S; AND CHEN, WT|
|Tipologia:||Articolo su rivista|
|Citazione:||GHERSI, G., ZHAO, Q., SALAMONE, M., YEH, Y., ZUCKER, S., & AND CHEN, W.T. (2006). The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices. CANCER RESEARCH, 66 (9), 4652-4661.|
|Digital Object Identifier (DOI):||10.1158/0008-5472.CAN-05-1245|
|Appare nelle tipologie:||01 - Articolo su rivista|