Zhao Y D, Springall D R, Hamid Q, Levene M, Polak J M
Department of Histochemistry, Royal Postgraduate Medical School, London, England.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S341-5.
We have demonstrated endothelin-1 (ET-1) binding sites in the blood vessels of human pulmonary tumors by in vitro autoradiography. The blood vessels of the tumors were confirmed by immunostaining with von Willebrand factor. Specific [125I]ET-1 binding was identified in the blood vessels of all sizes in both tumor and stromal tissues. Nonspecific binding was observed in squamous cell carcinomas and in carcinoids. The ET-1 binding in blood vessels was specific, saturable, and time-dependent. The binding reached equilibrium at 120 min. Scatchard analysis of [125I]ET-1 binding to sections of blood vessels of squamous cell carcinoma indicated binding to a single class of binding sites, with a dissociation constant (Kd) of 0.16 nM and a maximal density of binding sites (Bmax) of 126 amol/mm2. The binding was competitively inhibited by ET-1 >> VIC > ET-2 > sarafotoxin (SRb) > ET-3 but not by other unrelated peptides. Our results provide evidence that ET-1 binding is localized in the blood vessels of pulmonary tumors and in stromal tissues surrounding the tumor nest. ET may play a role in the angiogenesis of tumor growth.
我们通过体外放射自显影技术在人肺肿瘤血管中证实了内皮素-1（ET-1）结合位点。肿瘤血管通过用血管性血友病因子进行免疫染色得以确认。在肿瘤组织和间质组织的所有大小血管中均鉴定出特异性的[125I]ET-1结合。在鳞状细胞癌和类癌中观察到非特异性结合。血管中的ET-1结合具有特异性、可饱和性且呈时间依赖性。结合在120分钟时达到平衡。对鳞状细胞癌血管切片进行的[125I]ET-1结合的Scatchard分析表明，其与单一类别的结合位点结合，解离常数（Kd）为0.16 nM，最大结合位点密度（Bmax）为126 amol/mm2。该结合被ET-1 >> VIC > ET-2 > 蛙皮毒素（SRb）> ET-3竞争性抑制，但不受其他无关肽的抑制。我们的结果提供了证据，表明ET-1结合定位于肺肿瘤血管以及肿瘤巢周围的间质组织中。ET可能在肿瘤生长的血管生成中起作用。
