Zatelli M C, degli Uberti E C
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.
Dig Liver Dis. 2004 Feb;36 Suppl 1:S86-92. doi: 10.1016/j.dld.2003.11.018.
Somatostatin and its receptors are expressed in the thyroid gland, but somatostatin analogs which are currently available have provided contradictory results in the diagnosis and treatment of thyroid neoplasia. Somatostatin and its analogs fail to influence follicular thyroid function, whereas their administration in patients with medullary thyroid carcinoma induces a reduction of serum calcitonin concentrations and clinical symptoms, but fails to influence tumour size and patient survival rate. Radiolabelled somatostatin analogs can localise tumours expressing somatostatin receptors, but somatostatin receptor-targeted radiotherapy of thyroid malignancies has provided conflicting and inconclusive results. Our recent results indicate that somatostatin receptor 2 activation by somatostatin receptor 2 agonists inhibits cell proliferation in the human medullary thyroid carcinoma cell line, TT. This effect can be hampered by concurrent somatostatin receptor 5 selective agonist treatment, which fails to influence TT cell proliferation, suggesting an antagonism between somatostatin receptors 5 and 2 agonists in medullary thyroid carcinoma cells. Moreover, somatostatin receptors 2 or 5 agonists fail to inhibit calcitonin secretion and calcitonin gene expression. On the other hand, somatostatin receptor 1 agonists inhibit proliferation, calcitonin secretion and calcitonin gene expression in parafollicular C cells, suggesting that analogs with enhanced somatostatin receptor 1 affinity and selectivity besides having great potentiality as pharmacological tools to control neoplastic growth, may also be used to reduce symptoms in patients with medullary thyroid carcinoma.
生长抑素及其受体在甲状腺中表达，但目前可用的生长抑素类似物在甲状腺肿瘤的诊断和治疗中给出了相互矛盾的结果。生长抑素及其类似物不影响甲状腺滤泡功能，而在甲状腺髓样癌患者中使用它们会导致血清降钙素浓度降低和临床症状改善，但不影响肿瘤大小和患者生存率。放射性标记的生长抑素类似物可定位表达生长抑素受体的肿瘤，但针对甲状腺恶性肿瘤的生长抑素受体靶向放疗结果相互矛盾且尚无定论。我们最近的结果表明，生长抑素受体2激动剂激活生长抑素受体2可抑制人甲状腺髓样癌细胞系TT中的细胞增殖。同时进行生长抑素受体5选择性激动剂治疗会阻碍这种作用，该治疗不影响TT细胞增殖，这表明甲状腺髓样癌细胞中生长抑素受体5和2激动剂之间存在拮抗作用。此外，生长抑素受体2或5激动剂不能抑制降钙素分泌和降钙素基因表达。另一方面，生长抑素受体1激动剂可抑制甲状腺滤泡旁C细胞的增殖、降钙素分泌和降钙素基因表达，这表明除了作为控制肿瘤生长的药理学工具具有巨大潜力外，具有增强的生长抑素受体1亲和力和选择性的类似物还可用于减轻甲状腺髓样癌患者的症状。
