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Semin Thromb Hemost 2004; 30(1): 45-61
DOI: 10.1055/s-2004-822970
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Contact System and Angiogenesis: Potential for Therapeutic Control of Malignancy

Robert W. Colman1
  • 1Professor, The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania
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Publication History

Publication Date:
22 March 2004 (online)

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We have demonstrated that domain 5 (D5, kininostatin) and cleaved high-molecular-weight kininogen (HKa) inhibit endothelial proliferation, migration, and neovascularization in the in ovo chicken chorioallantoic membrane (CAM) assay, and that D5 and HKa act by stimulating apoptosis and interfering with the cell cycle at the G1-S transition. Both intact high-molecular-weight kininogen (HK) and low-molecular-weight kininogen induce angiogenesis in the CAM assay by releasing bradykinin. A monoclonal antibody, mAb C11C1, targeted to HK D5, inhibits FGF2- (fibroblast growth factor-2) and vascular endothelial growth factor-stimulated angiogenesis in the CAM assay by interfering with the binding of HK to endothelial cells. We also demonstrate the inhibitory effects of both mAb C11C1 and glutathione-S-transferase-D5 on the growth of a human tumor supplied by CAM vessels.

KEYWORDS

Kininogen - kininostatin - urokinase receptor - prekallikrein - angiogenesis

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Robert W ColmanM.D. 

The Sol Sherry Thrombosis Research Center, Temple University School of Medicine

3400 North Broad Street, Room 300 OMS

Philadelphia, PA 19140

Email: colmanr@astro.temple.edu

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