Generation of angiostatin-like fragments from plasminogen by prostate-specific antigen

Angiostatin, a potent inhibitor of angiogenesis, tumour growth and metastas is, is a biologically active fragment of plasminogen, containing the kringl e domains 1-4. It is generated from plasminogen by limited proteolysis, We show that prostate-specific antigen (PSA), a serine proteinase secreted by human prostate and human prostate cancer cells, is able to convert Lys-plas minogen to biologically active angiostatin-like fragments, containing kring les 1-4, by limited proteolysis of peptide bond Glu439-Ala440 in vitro. In an in vitro morphogenesis assay, the purified angiostatin-like fragments in hibited proliferation and tubular formation of human umbilical vein endothe lial cells with the same efficacy as angiostatin. This finding might help t o understand growth characteristics of prostate cancer, which usually has l ow microvessel density and slow proliferation. (C) 1999 Cancer Research Cam paign.