Padova H, Rubinfeld H, Hadani M, Cohen Z R, Nass D, Taylor J E, Culler M D, Shimon I
Institute of Endocrinology, Rabin Medical Center, Petah-Tiqva, Tel Aviv University, Sackler School of Medicine, Israel.
Mol Cell Endocrinol. 2008 May 14;286(1-2):214-8. doi: 10.1016/j.mce.2007.12.011. Epub 2007 Dec 27.
Clinically "non-functioning" human pituitary adenomas (NFPA) constitute about 35% of pituitary adenomas. Somatostatin receptors (SSTR) expression in these adenomas has previously been described both in vitro and in vivo, without evidence for a correlation with tumor volume or the therapeutic efficacy of somatostatin analogs. This study was performed on 13 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". In addition, 3 growth hormone (GH)-secreting adenomas served as controls. A specimen from each tumor was dispersed and digested to isolate and culture the tumor cells, and the in vitro effects of SSTR2 and SSTR5 selective analogs and Cortistatin (CST) (100nM) on cell viability were studied. The quantity of viable cells was estimated using the XTT method. RNA purification of tumor samples and subsequent RT-PCR studies for SSTR2 and SSTR5 expression were performed. Somatostatin analog with high affinity for SSTR2 reduced cell viability by 20-80% in 8 of 13 NFPAs studied, all expressing the SSTR2. The inhibitory effect on cell viability of SSTR5-selective analog was 15-80% in 10 of 13 NFPAs studied, all but three expressing the SSTR5. CST, however, effectively reduced cell viability in only 6 NFPAs. Cell viability was inhibited by all peptides studied in 2 out of 3 GH-secreting adenomas, expressing both receptors. The third adenoma responded to SSTR2 analog and expressed only SSTR2. These results suggest the involvement of SSTR2 and SSTR5 in the anti-proliferative effects of somatostatin; however, CST is less potent in reducing cell viability in these tumors.
临床上，“无功能”垂体腺瘤（NFPA）约占垂体腺瘤的35%。此前已有研究在体外和体内描述了这些腺瘤中生长抑素受体（SSTR）的表达情况，但未发现其与肿瘤体积或生长抑素类似物的治疗效果相关。本研究对13例手术切除的垂体大腺瘤进行了分析，这些腺瘤在术前被诊断为“无功能”。此外，选取3例分泌生长激素（GH）的腺瘤作为对照。将每个肿瘤的标本进行分散和消化，以分离并培养肿瘤细胞，研究SSTR2和SSTR5选择性类似物以及生长抑素（CST）（100nM）对细胞活力的体外影响。使用XTT法评估活细胞数量。对肿瘤样本进行RNA纯化，并随后进行SSTR2和SSTR5表达的RT-PCR研究。对13例NFPA中的8例进行研究，发现对SSTR2具有高亲和力的生长抑素类似物可使细胞活力降低20%-80%，所有这些NFPA均表达SSTR2。在13例NFPA中的10例中，SSTR5选择性类似物对细胞活力的抑制作用为15%-80%，除3例之外均表达SSTR5。然而，CST仅在6例NFPA中有效降低了细胞活力。在3例分泌GH的腺瘤中，有2例表达两种受体，所有研究的肽均抑制了其细胞活力。第三例腺瘤对SSTR2类似物有反应，且仅表达SSTR2。这些结果表明SSTR2和SSTR5参与了生长抑素的抗增殖作用；然而，CST在降低这些肿瘤细胞活力方面的作用较弱。
