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      Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.

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          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.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          0092-8674
          0092-8674
          Oct 21 1994
          : 79
          : 2
          Affiliations
          [1 ] Department of Surgery, Children's Hospital, Boston, Massachusetts.
          Article
          0092-8674(94)90200-3
          10.1016/0092-8674(94)90200-3
          7525077
          cfe77d72-0678-45cb-b99a-cb7ea78dfc63
          History

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