Secretion of MMP-9 by 1-LN human prostate tumor cells is modulated via a signaling mechanism initiated by interaction between plasminogen carbohydrate chains and DPP IV (CD26) on the cell surface
Remodeling of the extracellular matrix (ECM), which occurs during metastatic processes, is one of the requisite events for cellular invasion. Both the plasminogen (Pg) activation system and matrix metalloproteinases (MMPs) are involved in proteolytic degradation of ECM components which in turn alter cellular invasion. Secretion of MMP-9 (gelatinase B, 29 kDa progelatinase) is highly regulated at the transcriptional and post-translational levels. The mechanism of activation of the 92 kDa progelatinase into an active enzyme has not been entirety elucidated; although, plasmin (Pm) has been indirectly associated in a proteolytic cascade leading to the production of active MMP-9. Pg bound to the highly metastatic human prostate tumor cell line 1-LN is rapidly converted into Pm by receptor-bound urokinase-type Pg activator (uPA). This process induces a significant rise in cytosolk free Ca2+. We measured the secretion of MMPs in this system and found that active MMP-9 secretion may be regulated by this mechanism which involves first the interaction of Pm-carbohydrate chains with dipeptidyl peptidase IV (DPP IV), and then the coordinated enzymatic activity of both proteases. Our studies suggest a critical role for cell-surface Pg/Pm receptors in initiating signaling mechanisms which regulate MMP-9 secretion by 1-LN cells.
Gonzalez-Gronow, M; Weber, MR; Pizzo, SV
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