LOCALIZATION AND CHARACTERIZATION OF ENDOTHELIN-1 RECEPTOR-BINDING INTHE BLOOD-VESSELS OF HUMAN PULMONARY TUMORS

We have demonstrated endothelin-1 (ET-1) binding sites in the blood ve ssels of human pulmonary tumors by in vitro autoradiography. The blood vessels of the tumors were confirmed by immunostaining with von Wille brand factor. Specific [I-125]ET-1 binding was identified in the blood vessels of all sizes in both tumor and stromal tissues. Nonspecific b inding was observed in squamous cell carcinomas and in carcinoids. The ET-1 binding in blood vessels was specific, saturable, and time-depen dent. The binding reached equilibrium at 120 min. Scatchard analysis o f [I-125]ET-1 binding to sections of blood vessels of squamous cell ca rcinoma indicated binding to a single class of binding sites, with a d issociation constant (K-d) of 0.16 nM and a maximal density of binding sites (B-max) of 126 amol/mm(2). The binding was competitively inhibi ted by ET-1 much greater than VIC > ET-2 > sarafotoxin (SRb) > ET-3 bu t not by other unrelated peptides. Our results provide evidence that E T-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 t he angiogenesis of tumor growth.