Antiangiogenic Antithrombin

Michael S. O'Reilly

doi:10.1055/s-2007-991533

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2007; 33(7): 660-666
DOI: 10.1055/s-2007-991533

Antiangiogenic Antithrombin

Michael S. O'Reilly¹

¹Departments of Radiation Oncology and Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Abstract

ABSTRACT

Angiogenesis is critical for several physiologic and pathophysiologic processes, and several angiogenesis inhibitors are now in clinical trials for the treatment of cancer. Antithrombin is a member of the serpin family of proteins and functions as an inhibitor of thrombin and other enzymes involved in the clotting cascade. While studying the inhibition of tumor growth by tumor mass in a human small cell lung cancer model, we discovered that the cleaved conformation of antithrombin has potent antiangiogenic and antitumor activity. The stable locked and latent forms of intact antithrombin, which are substantially similar in conformation to the cleaved form of the molecule, also inhibit angiogenesis and tumor growth in vivo and act selectively upon endothelial cells and the tumor vasculature. The intact native molecule does not have this effect. The discovery of antiangiogenic antithrombin provides further evidence that the clotting and fibrinolytic pathways are directly related to the regulation of angiogenesis. As for other endogenous angiogenesis inhibitors, the precise mechanism of action for antiangiogenic antithrombin has not been defined, but several studies now suggest that it may target the endothelial cell at multiple levels resulting in a profound blockade of the angiogenic cascade. In this paper, an overview of the angiogenesis inhibitor antiangiogenic antithrombin and a summary of the pertinent literature are provided.

KEYWORDS

Antithrombin - angiogenesis - small cell lung cancer - malignancy - metastasis

Full Text

References

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Michael S O'ReillyM.D.

Department of Radiation Oncology, Unit 97, University of Texas M. D. Anderson Cancer Center

1515 Holcombe Boulevard, Houston, TX 77030

Email: moreilly@mdanderson.org