Zatelli Maria Chiara, Piccin Daniela, Tagliati Federico, Bottoni Arianna, Luchin Andrea, Vignali Cristina, Margutti Angelo, Bondanelli Marta, Pansini Gian Carlo, Pelizzo Maria Rosa, Culler Michael D, Degli Uberti Ettore C
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.
J Clin Endocrinol Metab. 2006 Jun;91(6):2218-24. doi: 10.1210/jc.2006-0334. Epub 2006 Mar 28.
Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. We previously demonstrated that somatostatin (SRIH) reduces cell growth in the human MTC cell line, TT, which expresses all SRIH receptor (SSTR) subtypes and responds differently to selective SSTR agonists.
To clarify the possible effects of SRIH analogs on hormone secretion and proliferation in MTC primary cultures, we evaluated SSTR expression and assessed the in vitro effects on calcitonin (CT) and chromogranin A secretion as well as cell viability of SRIH analogs interacting with SSTR1, SSTR2, and SSTR5.
Thirty-five patients affected by MTC were recruited from 2003 to 2005. After total thyroidectomy, the samples were examined for CT, chromogranin A, and SSTR expression by RT-PCR. Primary cultures were developed and tested with SRIH analogs interacting with SSTR1, SSTR2, and SSTR5.
We selected 18 MTC tumor samples, expressing SSTR1, SSTR2, and SSTR5. Two different groups were identified according to CT secretion inhibition by the clinically available SRIH analog, lanreotide. In the responder group, CT secretion was reduced by compounds interacting with SSTR1, SSTR2, and SSTR5, whereas cell viability was not affected. On the other hand, in the nonresponder group, CT secretion was reduced by the SSTR1 selective agonist, whereas cell viability was inhibited by SSTR2 selective agonists.
Our data suggest that SRIH analogs might be useful in medical therapy of MTC because they could have antiproliferative effects despite the lack of antisecretory activity and vice versa.
甲状腺髓样癌（MTC）是一种起源于甲状腺滤泡旁C细胞的罕见肿瘤。我们之前证明，生长抑素（SRIH）可降低人MTC细胞系TT中的细胞生长，该细胞系表达所有生长抑素受体（SSTR）亚型，并且对选择性SSTR激动剂有不同反应。
为了阐明SRIH类似物对MTC原代培养物中激素分泌和增殖的可能影响，我们评估了SSTR的表达，并评估了与SSTR1、SSTR2和SSTR5相互作用的SRIH类似物对降钙素（CT）和嗜铬粒蛋白A分泌以及细胞活力的体外影响。
2003年至2005年招募了35例MTC患者。全甲状腺切除术后，通过逆转录聚合酶链反应检测样本中的CT、嗜铬粒蛋白A和SSTR表达。建立原代培养物并用与SSTR1、SSTR2和SSTR5相互作用的SRIH类似物进行测试。
我们选择了18个表达SSTR1、SSTR2和SSTR5的MTC肿瘤样本。根据临床可用的SRIH类似物兰瑞肽对CT分泌的抑制作用，确定了两个不同的组。在反应组中，与SSTR1、SSTR2和SSTR5相互作用的化合物可降低CT分泌，而细胞活力不受影响。另一方面，在无反应组中，SSTR1选择性激动剂可降低CT分泌，而SSTR2选择性激动剂可抑制细胞活力。
我们的数据表明，SRIH类似物可能对MTC的医学治疗有用，因为它们可能具有抗增殖作用，尽管缺乏抗分泌活性，反之亦然。
