Colman Robert W
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Semin Thromb Hemost. 2004 Feb;30(1):45-61. doi: 10.1055/s-2004-822970.
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.
我们已经证明，结构域5（D5，激肽抑制素）和裂解的高分子量激肽原（HKa）在鸡胚绒毛尿囊膜（CAM）试验中可抑制内皮细胞增殖、迁移和新血管形成，并且D5和HKa通过刺激细胞凋亡以及在G（1）-S期转换时干扰细胞周期发挥作用。完整的高分子量激肽原（HK）和低分子量激肽原在CAM试验中均可通过释放缓激肽诱导血管生成。一种靶向HK D5的单克隆抗体mAb C11C1，在CAM试验中通过干扰HK与内皮细胞的结合，抑制成纤维细胞生长因子-2（FGF2）和血管内皮生长因子刺激的血管生成。我们还证明了mAb C11C1和谷胱甘肽-S-转移酶-D5对由CAM血管供应的人肿瘤生长均具有抑制作用。
