Abstract
Antithrombin, a member of the serpin family, functions as an inhibitor of thrombin and other enzymes. Cleavage of the carboxyl-terminal loop of antithrombin induces a conformational change in the molecule. Here it is shown that the cleaved conformation of antithrombin has potent antiangiogenic and antitumor activity in mouse models. The latent form of intact antithrombin, which is similar in conformation to the cleaved molecule, also inhibited angiogenesis and tumor growth. These data provide further evidence that the clotting and fibrinolytic pathways are directly involved in the regulation of angiogenesis.
Publication types
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Comment
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Antithrombins / chemistry
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Antithrombins / isolation & purification
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Antithrombins / metabolism
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Antithrombins / pharmacology*
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Carcinoma, Small Cell / blood supply
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Carcinoma, Small Cell / drug therapy
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Cell Line
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Culture Media, Conditioned
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Drug Screening Assays, Antitumor
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Humans
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Lung Neoplasms / blood supply
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Lung Neoplasms / drug therapy
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Mice
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Mice, SCID
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Neoplasm Transplantation
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Neovascularization, Pathologic / drug therapy*
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Protein Conformation
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Antithrombins
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Culture Media, Conditioned
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Peptide Fragments