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[Cancer Research 56, 4887-4890, November 1, 1996]
© 1996 American Association for Cancer Research
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Human Prostate Carcinoma Cells Express Enzymatic Activity That Converts Human Plasminogen to the Angiogenesis Inhibitor, Angiostatin1

Stephen Gately, Przemyslaw Twardowski, M. Sharon Stack, Matthew Patrick, Lisa Boggio, Deborah L. Cundiff, H. William Schnaper, Laird Madison, Olga Volpert, Noel Bouck, Jan Enghild, Hau C. Kwaan and Gerald A. Soff2

Division of Hematology/Oncology [S. G., P. T., M. P., L. B., D. L. C., G. A. S.], Department of Veterans Affairs Lakeside Medical Center [H. C. K.], Department of Obstetrics and Gynecology [M. S. S.], Department of Pediatrics, Children's Memorial Hospital [H. W. S.], Division of Endocrinology, Metabolism, and Molecular Medicine [L. M.], and Department of Microbiology-Immunology and R. H. Lurie Cancer Center [O. V., N. B.], Northwestern University School of Medicine, Chicago, Illinois 60611, and Department of Pathology [J. E.], Duke University, Durham, North Carolina 27710

Angiostatin is an inhibitor of angiogenesis and metastatic growth that is found in tumor-bearing animals and can be generated in vitro by the proteolytic cleavage of plasminogen. The mechanism by which angiostatin 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 purified human plasminogen or plasmin. Affinity purified PC-3-derived angiostatin inhibited human endothelial cell proliferation, basic fibroblast growth factor-induced migration, endothelial cell tube formation, and basic fibroblast growth factor-induced corneal angiogenesis. Studies with proteinase inhibitors demonstrated that a serine proteinase is necessary for angiostatin generation. These data indicate that bioactive angiostatin can be generated directly by human prostate cancer cells and that serine proteinase activity is necessary for angiostatin generation.

1 This work supported in part by The Feinberg Cardiovascular Research Institute, a grant-in-aid from the American Cancer Society, IL Division (to G. A. S.), Veterans Administration Merit Review Research Grant (H. C. K.), and NIH Grants CA58900 (M. S. S.) and CA52750 and CA64239 (N. B.).

2 To whom requests for reprints should be addressed, at Division of Hematology/Oncology, 303 East Chicago Avenue, Searle Building Suite 3-565, Chicago, Illinois, 60611.

Received 8/22/96. Accepted 9/18/96.




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