title: Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.
abstract: The phenomenon of inhibition of tumor growth by tumor mass has been repeatedly studied, but without elucidation of a satisfactory mechanism. In our animal model, a primary tumor inhibits its remote metastases. After tumor removal, metastases neovascularize and grow. When the primary tumor is present, metastatic growth is suppressed by a circulating angiogenesis inhibitor. Serum and urine from tumor-bearing mice, but not from controls, specifically inhibit endothelial cell proliferation. The activity copurifies with a 38 kDa plasminogen fragment that we have sequenced and named angiostatin. A corresponding fragment of human plasminogen has similar activity. Systemic administration of angiostatin, but not intact plasminogen, potently blocks neovascularization and growth of metastases. We here show that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin.
authors.affiliation: Department of Surgery, Children's Hospital, Boston, Massachusetts.
authors.forename: M S
authors.initials: MS
authors.lastname: O'Reilly
authors.forename: L
authors.initials: L
authors.lastname: Holmgren
authors.forename: Y
authors.initials: Y
authors.lastname: Shing
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: R A
authors.initials: RA
authors.lastname: Rosenthal
authors.forename: M
authors.initials: M
authors.lastname: Moses
authors.forename: W S
authors.initials: WS
authors.lastname: Lane
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: E H
authors.initials: EH
authors.lastname: Sage
authors.forename: J
authors.initials: J
authors.lastname: Folkman
mesh_terms: D000595:Amino Acid Sequence; D043168:Angiostatins; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000098:blood supply* / Q000473:pathology; D002417:Cattle; D004730:Endothelium, Vascular / Q000166:cytology; D006131:Growth Inhibitors / Q000097:blood* / Q000652:urine*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000494:pharmacology*; D010958:Plasminogen / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006131:Growth Inhibitors; D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen