Colman Robert W
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
Int Immunopharmacol. 2002 Dec;2(13-14):1887-94. doi: 10.1016/s1567-5769(02)00173-x.
High molecular weight kininogen (HK) exhibits two activities with respect to angiogenesis after cleavage by plasma kallikrein. Cleaved HK (HKa) and its cell-binding domain 5 (D5), kininostatin, are potent antiangiogenic polypeptides. They inhibit endothelial cell migration, proliferation and tube formation. HKa and D5 inhibit angiogenesis in the chicken chorioallantoic membrane (CAM) assay. D5 stimulates apoptosis and interferes with the cell cycle. In contrast, intact HK is proangiogenic by liberating bradykinin. A monoclonal antibody to HK can inhibit angiogenesis in the CAM assay, human colon carcinoma growing as a xenograft in nude mice, and murine hybridomas growing in syngeneic hosts. Not only are the tumors decreased in volume and weight to isotype controls but the mean vascular density is decreased. Thus, both D5 and its constituent peptide and monoclonal antibody have potential for inhibiting angiogenesis and tumor growth in human therapy.
高分子量激肽原（HK）在被血浆激肽释放酶裂解后，在血管生成方面表现出两种活性。裂解后的HK（HKa）及其细胞结合域5（D5）即激肽抑制素，是强效的抗血管生成多肽。它们抑制内皮细胞迁移、增殖和管腔形成。HKa和D5在鸡胚绒毛尿囊膜（CAM）试验中抑制血管生成。D5刺激细胞凋亡并干扰细胞周期。相反，完整的HK通过释放缓激肽而具有促血管生成作用。一种针对HK的单克隆抗体在CAM试验、裸鼠异种移植生长的人结肠癌以及同基因宿主中生长的鼠杂交瘤中均可抑制血管生成。不仅肿瘤的体积和重量相较于同型对照有所减小，而且平均血管密度也降低。因此，D5及其组成肽以及单克隆抗体在人类治疗中均具有抑制血管生成和肿瘤生长的潜力。
