Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines

The ability of a cell to modify the extracellular matrix is important in se veral pathophysiological alterations including tumorigenesis. Cell transfor mation is accompanied by changes in the surrounding stroma as a result of t he action of specific proteases such as the urokinase plasminogen activator (uPA), which has been associated with invasive potential in many tumor typ es. In this study, we analyzed the release of vesicle-associated uPA by the aggressive prostatic carcinoma cell line PC3 and the implications of this release for the invasive behaviour of prostatic tumor cells. Zymography and Western blot analysis revealed the presence of vesicle-associated uPA in t he high-molecular weight form. Vesicles adhered to and degraded both collag en IV and reconstituted basal membrane (Matrigel), and plasminogen enhanced the degradation in a dose-dependent manner. Addition of membrane vesicles shed by PC3 cells to cultures of the poorly invasive prostate cancer cell l ine LnCaP enhanced the adhesive and invasive capabilities of the latter, su ggesting a mechanism involving substrate recognition and degradation. Toget her, these findings indicate that membrane vesicles can promote tumor invas ion and point to the important role of vesicle-associated uPA in the extrac ellular compartment.