Interaction of plasminogen with dipeptidyl peptidase IV initiates a signaltransduction mechanism which regulates expression of matrix metalloproteinase-9 by prostate cancer cells

Both plasminogen (Pg) activation and matrix metalloproteinases (MMPs) are i nvolved in the proteolytic degradation of extracellular matrix components, a requisite event for malignant cell metastasis, The highly invasive 1-LN h uman prostate tumour cell line synthesizes and secretes large amounts of Pg activators and MMPs. We demonstrate here that the Pg type 2 (Pg 2) recepto r in these cells is composed primarily of the membrane glycoprotein dipepti dyl peptidase IV (DPP IV). Pg 2 has six glycoforms that differ in their sia lic acid content, Only the highly sialylated Pg 2 gamma, Pg 2 delta and Pg 2 epsilon glycoforms bind to DPP IV via their carbohydrate chains and induc e a Ca2+ signalling cascade; however, Pg 2 epsilon alone is also able to si gnificantly stimulate expression of MMP-9. We further demonstrate that the Pg-mediated invasive activity of 1-LN cells is dependent on the availabilit y of Pg 2 epsilon, This is the first demonstration of a direct association between the expression of MMP-9 and the Pg activation system.