Srkalovic G, Cai R Z, Schally A V
Endocrine, Polypeptide, and Cancer Institute, Veterans Administration Medical Center, New Orleans, Louisiana.
J Clin Endocrinol Metab. 1990 Mar;70(3):661-9. doi: 10.1210/jcem-70-3-661.
The binding characteristics of several somatostatin (SS-14) analogs developed in our laboratory were examined in various human and animal tumors and normal tissues. In rat cerebral cortex and human breast cancer membranes the interaction of SS-14 with its binding sites was rapid, specific, saturable, linear with protein concentrations, and dependent on time and temperature. Analysis of kinetic and equilibrium experimental data showed that the interaction of [125I-Tyr11]SS-14 with the binding sites in all normal and tumoral tissue specimens was consistent with the presence of a single class of noncooperative binding sites. Superactive octapeptide analogs of somatostatin-containing hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys showed significant binding affinities to SS-14 receptors. Among these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I) showed the highest binding affinity to normal human pancreatic tissue and human pancreatic adenocarcinoma. In contrast, Sandostatin (SMS 201-995) bound only to normal pancreas, not to human pancreatic cancers. Analog RC-98-I also showed a high binding to human and rat prostate cancers. In human epithelial ovarian cancers and an arrhenoblastoma, analogs D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2 (RC-95-I), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) appeared to be the most potent in displacing labeled SS-14. Analogs Ac-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-101-I) as well as RC-121, RC-160, and RC-95-I, but not SMS-201-995, showed high binding affinity in human breast cancers. In specimens of human meningioma the highest binding was found with analogs RC-121, RC-95-I, and RC-101-I. Since marked variations in binding affinities were noted for several analogs in the tissues of origin and the tumors, this suggest that differences may exist between somatostatin receptors not only in normal vs. cancerous tissues, but also among various tumors. Our findings also imply that some analogs could be therapeutically superior to others in the treatment of certain tumors.
我们实验室研发的几种生长抑素（SS - 14）类似物的结合特性，在多种人类和动物肿瘤以及正常组织中进行了检测。在大鼠大脑皮层和人乳腺癌细胞膜中，SS - 14与其结合位点的相互作用迅速、特异、可饱和、与蛋白质浓度呈线性关系，且依赖于时间和温度。动力学和平衡实验数据分析表明，[125I - Tyr11]SS - 14与所有正常和肿瘤组织标本中结合位点的相互作用，与单一类别的非协同结合位点的存在一致。含六肽序列Cys - Phe - D - Trp - Lys - Thr - Cys或Cys - Tyr - D - Trp - Lys - Val - Cys的生长抑素超活性八肽类似物，对SS - 14受体显示出显著的结合亲和力。在这些类似物中，D - Trp - Cys - Phe - D - Trp - Lys - Thr - Cys - Thr - NH2（RC - 98 - I）对正常人胰腺组织和人胰腺腺癌显示出最高的结合亲和力。相比之下，善得定（SMS 201 - 995）仅与正常胰腺结合，不与人胰腺癌结合。类似物RC - 98 - I对人及大鼠前列腺癌也显示出高结合力。在人上皮性卵巢癌和卵巢支持间质细胞瘤中，类似物D - Phe - Cys - Phe - D - Trp - Lys - Thr - Cys - Trp - NH2（RC - 95 - I）、D - Phe - Cys - Tyr - D - Trp - Lys - Val - Cys - Thr - NH2（RC - 121）和D - Phe - Cys - Tyr - D - Trp - Lys - Val - Cys - Trp - NH2（RC - 160）在取代标记的SS - 14方面似乎最为有效。类似物Ac - Phe - Cys - Phe - D - Trp - Lys - Thr - Cys - Thr - NH2（RC - 101 - I）以及RC - 121、RC - 160和RC - 95 - I，但不包括SMS - 201 - 995，在人乳腺癌中显示出高结合亲和力。在人脑膜瘤标本中，类似物RC - 121、RC - 95 - I和RC - 101 - I的结合力最高。由于在起源组织和肿瘤中，几种类似物的结合亲和力存在显著差异，这表明生长抑素受体不仅在正常组织与癌组织之间可能存在差异，而且在各种肿瘤之间也可能存在差异。我们的研究结果还表明，在某些肿瘤的治疗中，一些类似物可能在治疗效果上优于其他类似物。
