HUMAN PROSTATE CARCINOMA-CELLS EXPRESS ENZYMATIC-ACTIVITY THAT CONVERTS HUMAN PLASMINOGEN TO THE ANGIOGENESIS INHIBITOR, ANGIOSTATIN

Angiostatin is an inhibitor of angiogenesis and metastatic growth that is found in tumor-bearing animals and can be generated in vitro by th e proteolytic cleavage of plasminogen. The mechanism by which angiosta tin is produced in vivo has not been defined. We now demonstrate that human prostate carcinoma cell lines (PC-3, DU-145, and LN-CaP) express enzymatic activity that can generate bioactive angiostatin from purif ied human plasminogen or plasmin. Affinity purified PC-3-derived angio statin inhibited human endothelial cell proliferation, basic fibroblas t growth factor-induced migration, endothelial cell tube formation, an d basic fibroblast growth factor-induced corneal angiogenesis. Studies with proteinase inhibitors demonstrated that a serine proteinase is n ecessary for angiostatin generation. These data indicate that bioactiv e angiostatin can be generated directly by human prostate cancer cells and that serine proteinase activity is necessary for angiostatin gene ration.