Miller G V, Farmery S M, Woodhouse L F, Primrose J N
University Department of Surgery, St. James's University Hospital, Leeds, UK.
Br J Cancer. 1992 Aug;66(2):391-5. doi: 10.1038/bjc.1992.275.
Somatostatin is a regulatory peptide implicated in the control of cellular proliferation in epithelial tissues and this regulation may occur directly via membrane bound receptor activation. The aim of this study was to investigate somatostatin binding in human gastrointestinal cancer and normal mucosa. Plasma membranes were prepared from specimens of tumour and normal mucosa from 51 patients undergoing surgical resection for malignancy (28 gastric, 23 colorectal). Using a competitive displacement assay, specific 125I-tyrosine-11-somatostatin-14 binding to plasma membranes was assessed and and characterised in terms of receptor affinity (Kd) and maximum binding capacity (Bmax) as determined by Scatchard analysis. Specific low affinity (Kd = 166 nM), high capacity (Bmax = 1.2 pmol mg-1 protein) somatostatin binding was demonstrated in 22 of the gastric cancers and 17 of the colorectal cancers (Kd = 140 nM, Bmax = 1.8 pmol mg-1 protein). Similar affinity and binding capacity was demonstrable in normal mucosal samples. High affinity receptors for somatostatin were expressed by one gastric carcinoma (Kd = 0.9 nM; Bmax = 0.23 pmol mg-1 protein). Thus, low affinity, high capacity binding is a common feature of gastrointestinal tumours and normal mucosa, and high affinity receptors may occasionally be demonstrated. The functional significance of these low affinity binding sites requires elucidation to determine whether long-acting somatostatin analogues may have therapeutic benefit in gastrointestinal malignancy.
生长抑素是一种调节肽，参与上皮组织细胞增殖的控制，这种调节可能通过膜结合受体激活直接发生。本研究的目的是调查生长抑素在人类胃肠道癌和正常黏膜中的结合情况。从51例因恶性肿瘤接受手术切除的患者（28例胃癌、23例结直肠癌）的肿瘤和正常黏膜标本中制备质膜。使用竞争性置换分析，评估并通过Scatchard分析确定的受体亲和力（Kd）和最大结合容量（Bmax）来表征特异性125I - 酪氨酸 - 11 - 生长抑素 - 14与质膜的结合。在22例胃癌和17例结直肠癌中证实了特异性低亲和力（Kd = 166 nM）、高容量（Bmax = 1.2 pmol mg-1蛋白质）的生长抑素结合（Kd = 140 nM，Bmax = 1.8 pmol mg-1蛋白质）。在正常黏膜样本中也显示出类似的亲和力和结合容量。一例胃癌表达了生长抑素的高亲和力受体（Kd = 0.9 nM；Bmax = 0.23 pmol mg-1蛋白质）。因此，低亲和力、高容量结合是胃肠道肿瘤和正常黏膜的共同特征，高亲和力受体偶尔也可能出现。这些低亲和力结合位点的功能意义需要阐明，以确定长效生长抑素类似物在胃肠道恶性肿瘤中是否可能具有治疗益处。
