Presence of membrane binding sites for [D-TRP6]-luteinizing hormone-releasing hormone in experimental pancreatic cancer.
Presence of membrane binding sites for [D-TRP6]-luteinizing hormone-releasing hormone in experimental pancreatic cancer.
复制标题
实验性胰腺癌中存在 [D-TRP6]-黄体生成素释放激素的膜结合位点。
DOI：
10.1016/0304-3835(89)90141-9
复制
发表时间：
1989
期刊：
影响因子：
9.7
通讯作者：
Schally,AV
中科院分区：
文献类型：
--
作者：
Fekete,M;Zalatnai,A;Schally,AV
研究了N-亚硝基双(2-氧丙基)胺(BOP)诱导的仓鼠胰腺癌细胞膜[D-Trp6]-黄体生成素释放激素([D-Trp6]-Lh-RH)、生长抑素(SS-14)和表皮生长因子(EGF)的结合部位特征(解离常数Kd和最大结合容量Bmax)。完整的正常仓鼠胰腺未显示[D-Trp6]-Lh-RH结合部位，但BOP诱发胰腺癌后发现低亲和力、高容量的[D-Trp6]-Lh-RH结合部位。正常胰腺组织和胰腺癌组织中均存在高亲和力、低亲和力的SS-14和EGF结合部位。与胰腺癌相比，正常仓鼠胰腺组织中SS-14结合位点数显著升高，而EGF结合位点数显著降低。用激动剂[D-Trp6]-LH-RH和生长抑素类似物-RC-160微囊单独或联合治疗荷胰腺癌的仓鼠，可引起肿瘤的组织病理学消退，同时降低[D-Trp6]-LH-RH的Kd值和Bmax，增加SS-14结合位点的Bmax。这些发现首次证明了[D-Trp6]-Lh-RH在胰腺癌中的结合部位。我们的结果还表明，[D-Trp6]-LH-RH和RC-160对胰腺癌的抑制作用不仅可以通过抑制性激素、胃肠激素和生长因子间接介导，还可以直接作用于肿瘤膜上的特定结合部位。
Characteristics of binding sites (dissociation constant: Kdand maximal binding capacity: Bmax) for [D-Trp6]-luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH]), somatostatin (SS-14) and epidermal growth factor (EGF) were evaluated in membrane fractions of N-Nitrosobis (2-oxopropyl) amine (BOP)-induced pancreatic adenocarcinoma of hamsters. Intact, normal hamster pancreata did not show any binding sites for [D-Trp6]-LH-RH, but specific [D-Trp6]-LH-RH binding sites with low affinity and high capacity were found after pancreatic cancer was induced with BOP. Membrane binding sites for SS-14 and EGF, with high affinity and low capacity were present, both in normal and cancerous pancreata. Normal hamster pancreatic tissue had significantly higher levels of SS-14 binding sites and lower concentration of EGF binding sites as compared to pancreatic carcinoma. In vivo treatment of hamsters bearing pancreatic cancers with microcapsules of agonist [D-Trp6]-LH-RH and the somatostatin analog-RC-160 alone, or in combination, caused histopathological regression of tumors and concomitantly decreased the Kdand Bmaxof [D-Trp6]-LH-RH, and increased the Bmaxof the SS-14 binding sites. These findings represent the first demonstration of binding sites for [D-Trp6]-LH-RH in pancreatic cancers. Our results also suggest that tumor inhibitory effects of [D-Trp6]-LH-RH and RC-160 in pancreatic cancer could be mediated not only indirectly through suppression of sex-steroids, gastrointestinal hormones and growth factors, but also directly by an action on specific binding sites located on the tumor membranes.