Journal Article

Antiangiogenic Activity of the Cleaved Conformation of the Serpin Antithrombin

O'Reilly, Michael S., Lane, William S., Folkman, Judah, Pirie-Shepherd, Steven

1999

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / Antineoplastic Agents - chemistry / Antineoplastic Agents - isolation & purification / Antineoplastic Agents - metabolism / Antineoplastic Agents - pharmacology / Antithrombins / Antithrombins - chemistry / Antithrombins - isolation & purification / Antithrombins - metabolism / Antithrombins - pharmacology / Biological and medical sciences / Cancer / Carcinoma, Small Cell - blood supply / Carcinoma, Small Cell - drug therapy / Cell Line / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Control Groups / Culture Media, Conditioned / Drug Screening Assays, Antitumor / Enzymes / Evidence / Fundamental and applied biological sciences. Psychology / Humans / Inhibition / Lung Neoplasms - blood supply / Lung Neoplasms - drug therapy / Mice / Mice, SCID / Molecular and cellular biology / Molecules / Neoplasm Transplantation / Neovascularization, Pathologic - drug therapy / Peptide Fragments - chemistry / Peptide Fragments - metabolism / Peptide Fragments - pharmacology / Protein Conformation / Rodents / Tumor Cells, Cultured / Tumors