Hofland L J, Lamberts S W
Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.
Baillieres Clin Endocrinol Metab. 1996 Jan;10(1):163-76. doi: 10.1016/s0950-351x(96)80362-4.
A variety of human neuroendocrine tumours express SSTR. The five recently cloned human SSTR subtypes have a distinct chromosomal localization and pharmacological profile, and a tissue-specific expression pattern which suggests a differential function of SSTR subtypes in different organ systems. Most tumours carrying SSTR may express multiple SSTR subtypes, while the SSTR2 subtype is most predominantly expressed. The somatostatin analogue, octreotide, binds with high affinity to the SSTR2 and SSTR5 subtype and with a low affinity to the SSTR3 subtype. This analogue does not bind to the SSTR1 and SSTR4 subtypes. No major differences in the binding characteristics have been found between octreotide and two other clinically used octapeptide SST-analogues, BIM-23014 and RC-160. Our preliminary data indicate that an absent hormonal response to octreotide in vitro also implies an absent response to BIM-23014 and RC-160. The expression of the SSTR2 subtype in human tumours is proposed to be related to a clinical beneficial effect of octreotide treatment, while the functional significance of the other SSTR subtypes is not clear at present. In addition it is unclear which subtype(s) is involved in the antimitotic actions of SST(-analogues). Further developments with regard to the oncological application of SST analogues await the identification of the SSTR subtype(s) mediating anti-proliferative effects, as well as the development of analogues which selectively activate this subtype(s). A good correlation has been found between the presence of SSTR2 subtype mRNA and binding of [125I-Tyr3]octreotide in human primary tumours. Therefore, SSTR scintigraphy of human primary tumours and their metastases presumably visualizes SSTR2-expressing tumours, although it is reasonable to assume that SSTR5, and to a lesser extent SSTR3, when expressed simultaneously with SSTR2, also contribute to the visualization of tumours.
多种人类神经内分泌肿瘤表达生长抑素受体（SSTR）。最近克隆出的5种人类SSTR亚型具有不同的染色体定位和药理学特征，以及组织特异性表达模式，这表明SSTR亚型在不同器官系统中具有不同功能。大多数携带SSTR的肿瘤可能表达多种SSTR亚型，其中SSTR2亚型表达最为突出。生长抑素类似物奥曲肽与SSTR2和SSTR5亚型具有高亲和力，与SSTR3亚型具有低亲和力。该类似物不与SSTR1和SSTR4亚型结合。在奥曲肽与另外两种临床使用的八肽SST类似物BIM - 23014和RC - 160之间，未发现结合特性有重大差异。我们的初步数据表明，体外对奥曲肽无激素反应也意味着对BIM - 23014和RC - 160无反应。人类肿瘤中SSTR2亚型的表达被认为与奥曲肽治疗的临床有益效果相关，而目前其他SSTR亚型的功能意义尚不清楚。此外，目前尚不清楚哪种亚型参与了SST（类似物）的抗有丝分裂作用。关于SST类似物在肿瘤学应用方面的进一步发展，有待于鉴定介导抗增殖作用的SSTR亚型，以及开发选择性激活该亚型的类似物。已发现人类原发性肿瘤中SSTR2亚型mRNA的存在与[125I - Tyr3]奥曲肽的结合之间存在良好的相关性。因此，人类原发性肿瘤及其转移灶的SSTR闪烁扫描可能显示表达SSTR2的肿瘤，尽管合理推测当SSTR5以及在较小程度上SSTR3与SSTR2同时表达时，也有助于肿瘤的显影。
