Preston S R, Woodhouse L F, Jones-Blackett S, Wyatt J I, Primrose J N
Academic Unit of Surgery, St. James's University Hospital, Leeds, United Kingdom.
Cancer Res. 1993 Nov 1;53(21):5090-2.
The bombesin-like peptides gastrin releasing peptide (GRP) and neuromedin B are found in the submucosal and myenteric plexuses of the human gastrointestinal tract. These peptides are potent mitogens to Swiss 3T3 fibroblasts and are important autocrine growth factors in human small cell lung cancer cells. We have recently described the presence of receptors for the bombesin-like peptide, GRP, on the human gastric cancer cell line St42. In this study, we examined fresh resected gastric cancer and uninvolved mucosa from 23 patients for the presence of binding sites to the bombesin-like peptides. Thirteen of 23 gastric cancers expressed high affinity binding sites for bombesin (mean Kd = 3.42 nM; mean Bmax = 40.5 pmol/mg protein), of which 12 were subsequently characterized and found to be of the GRP-preferring subtype. One of 23 mucosal samples specifically bound bombesin and was the only sample from a patient with Ménétrier's disease, a disorder of mucosal growth known to be premalignant. The early gastric cancer from this patient also possessed high affinity binding sites for GRP. This is the first description of binding sites to bombesin-like peptides on human gastric cancer and Ménétrier's mucosa. The role of bombesin/GRP antagonists in the treatment of gastric cancer warrants investigation.
胃泌素释放肽（GRP）和神经降压素B等蛙皮素样肽存在于人类胃肠道的黏膜下神经丛和肌间神经丛中。这些肽是瑞士3T3成纤维细胞的强效促有丝分裂原，并且是人类小细胞肺癌细胞重要的自分泌生长因子。我们最近报道了在人胃癌细胞系St42上存在蛙皮素样肽GRP的受体。在本研究中，我们检测了23例患者新鲜切除的胃癌组织及未受累黏膜中蛙皮素样肽结合位点的存在情况。23例胃癌组织中有13例表达了对蛙皮素的高亲和力结合位点（平均解离常数Kd = 3.42 nM；平均最大结合容量Bmax = 40.5 pmol/mg蛋白），其中12例随后被鉴定并发现为偏好GRP的亚型。23例黏膜样本中有1例特异性结合蛙皮素，该样本来自一名患有梅内特里耶病的患者，梅内特里耶病是一种已知的癌前黏膜生长紊乱疾病。该患者的早期胃癌也具有GRP的高亲和力结合位点。这是首次报道人胃癌和梅内特里耶病黏膜上蛙皮素样肽结合位点的情况。蛙皮素/GRP拮抗剂在胃癌治疗中的作用值得研究。
