Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors
Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors
复制标题
DOI：
10.1007/s12020-017-1482-3
复制
发表时间：
2018-02-01
期刊：
影响因子：
3.7
通讯作者：
Castano, Justo P.
中科院分区：
文献类型：
--
作者：
Herrera-Martinez, Aura D.;Gahete, Manuel D.;Castano, Justo P.
胃肠胰神经内分泌肿瘤（GEP-NETs）是一种异质性的恶性肿瘤，通常在诊断时表现为转移，其临床结果难以预测。生长抑素（SST）类似物（SSAs）提供了一种有价值的药理学工具来缓解激素症状，并控制一些NETs的进展。然而，许多患者对SST没有反应或产生耐药性，并且在GEP-NETs中SST及其受体（sst1-sst5）的病理生理存在许多不确定性。测定GEP-NETs中SST系统组分的表达，并与非肿瘤邻近组织和正常组织进行比较，并与临床和组织学特征相关。具体来说，58例GEP-NETs患者和14例正常样本被纳入研究。NET细胞系的细胞活力是通过对特定SSAs的响应来测定的。正常样本和非肿瘤邻近组织表达谱相似，sst2和sst3表达明显，其他受体表达较低。相比之下，皮质抑素、sst1、sst4和sst5在肿瘤中过表达，而sst3和sst4在分化程度较低的肿瘤中似乎过表达。一些SST系统成分与血管/神经的侵袭和转移有关。体外，sst1和sst3激动剂降低BON-1细胞的活力，而与奥曲肽和pasireotide类似，它们提高QGP-1细胞的活力。这些结果提供了关于GEP-NETs的SST系统病理生理学的新信息，包括与临床组织学参数的相关信息，这可能有助于更好地理解NETs的内在异质性，并确定对GEP-NETs患者具有潜在预后和/或治疗价值的新生物标志物和/或靶点。
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of malignancies often presenting with metastasis at diagnosis and whose clinical outcome is difficult to predict. Somatostatin (SST) analogs (SSAs) provide a valuable pharmacological tool to palliate hormonal symptoms, and control progression in some NETs. However, many patients do not respond to SSAs or develop resistance, and there are many uncertainties regarding pathophysiology of SST and its receptors (sst1-sst5) in GEP-NETs.The expression of SST system components in GEP-NETs was determined, compared with that of non-tumor adjacent and normal tissues and correlated with clinical and histological characteristics. Specifically, 58 patients with GEP-NETs and 14 normal samples were included. Cell viability in NET cell lines was determined in response to specific SSAs.Normal samples and non-tumor adjacent tissues presented a similar expression profile, with appreciable expression of sst2 and sst3, and a lower expression of the other receptors. In contrast, cortistatin, sst1, sst4, and sst5 were overexpressed in tumors, while sst3 and sst4 seemed overexpressed in less differentiated tumors. Some SST system components were related to vascular/nerve invasion and metastasis. In vitro, sst1 and sst3 agonists reduced viability in BON-1 cells, while they, similar to octreotide and pasireotide, increased viability in QGP-1 cells.These results provide novel information on SST system pathophysiology in GEP-NETs, including relevant associations with clinical-histological parameters, which might help to better understand the intrinsic heterogeneity of NETs and to identify novel biomarkers and/or targets with potential prognostic and/or therapeutic value for GEP-NETs patients.