The contact system and angiogenesis: potential for therapeutic control of malignancy.
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 G (1)-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.
Colman
Robert W
RW
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. colmanr@astro.temple.edu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D007704:Kininogens / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011288:Prekallikrein / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator
D000911:Antibodies, Monoclonal; D007704:Kininogens; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011288:Prekallikrein