Hemostatic Regulators of Tumor Angiogenesis: A Source of Antiangiogenic Agents for Cancer Treatment?

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Abstract
The maintenance of vascular integrity and control of blood loss are regulated by a sophisticated system of circulating and cell-associated hemostatic factors. These factors control local platelet aggregation, the conversion of soluble fibrino- gen to an insoluble fibrin polymer, and the dissolution of fibrin. However, hemostatic factors are also involved in a number of physiologic processes, including development, tis- sue remodeling, wound repair, reproduction, inflammation, and angiogenesis. In this review, we outline ways in which angiogenesis is coordinated with and regulated by hemosta- sis. We focus on inhibitors of angiogenesis contained within platelets or harbored as cryptic fragments of hemostatic proteins and assess the experimental and preclinical evi- dence for their ability to inhibit tumor angiogenesis and, thus, their potential to be anticancer agents. Finally, we review the results of recent clinical trials involving angio- genesis inhibitors and the evidence that antiangiogenic ther- apy may be associated with hemostatic complications. (J Natl Cancer Inst 2003;95:1660 -73)

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