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生长抑素受体2在犬脑膜瘤中的表达

Somatostatin Receptor 2 Expression in Canine Meningioma.

作者信息

Foiani G, Guelfi G, Chiaradia E, Mancini F, Trivelli C, Vitellozzi G, Lepri E, Mandara M T

机构信息

Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, Perugia, Italy.

Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, Perugia, Italy.

出版信息

J Comp Pathol. 2019 Jan;166:59-68. doi: 10.1016/j.jcpa.2018.11.002. Epub 2018 Dec 13.

Abstract

The neuropeptide somatostatin (SST) plays an important regulatory role in the proliferation of normal and neoplastic cells. Five subtypes of somatostatin receptors (SSTRs), SSTR1-SSTR5, have been identified in human tumours. The SSTR2 subtype is identified most commonly in meningiomas. Long half-life SST analogues are now recommended for the systemic treatment of unresectable or radiation-refractory recurrent human meningiomas. In this study, SSTR2 expression was evaluated in 46 canine meningiomas; in 21 cases this was by immunohistochemistry and in 25 cases by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). In addition, SSTR2 expression was evaluated by immunocytochemistry, western blotting and RT-qPCR on primary cell cultures prepared from two canine meningiomas. SSTR2 immunohistochemical expression was observed in 17/21 cases (81%), and SSTR2 mRNA expression was detected in 14/25 cases (56%). SSTR2 protein and gene expression were not significantly correlated with the tumour histological subtype or grade. Overall, meningothelial meningiomas showed constant and diffuse SSTR2 immunohistochemical expression and the highest SSTR2 gene expression level compared with other subtypes. A tendency for loss of SSTR2 in high-grade meningiomas was observed in both immunohistochemical and RT-qPCR studies. About 90% of cultured canine meningioma cells showed SSTR2 expression. In both of the meningioma cell cultures, SSTR2 expression was also detected by western blotting and RT-qPCR. This study demonstrates for the first time that canine meningioma expresses SSTR2 and that this expression is maintained in vitro. Our results, while preliminary, provide encouragement for further studies aimed at finding novel medical treatment strategies for canine meningioma, especially for tumours that are not surgically accessible.

摘要

神经肽生长抑素(SST)在正常细胞和肿瘤细胞的增殖中发挥着重要的调节作用。在人类肿瘤中已鉴定出5种生长抑素受体(SSTRs)亚型,即SSTR1 - SSTR5。SSTR2亚型在脑膜瘤中最为常见。目前推荐使用长半衰期的SST类似物对不可切除或放疗难治性复发性人类脑膜瘤进行全身治疗。在本研究中,对46例犬脑膜瘤进行了SSTR2表达评估;其中21例通过免疫组织化学评估,25例通过逆转录定量聚合酶链反应(RT-qPCR)评估。此外,还通过免疫细胞化学、蛋白质印迹法和RT-qPCR对从两个犬脑膜瘤制备的原代细胞培养物进行了SSTR2表达评估。在17/21例(81%)中观察到SSTR2免疫组织化学表达,在14/25例(56%)中检测到SSTR2 mRNA表达。SSTR2蛋白和基因表达与肿瘤组织学亚型或分级无显著相关性。总体而言,与其他亚型相比,脑膜内皮型脑膜瘤显示出持续且弥漫的SSTR2免疫组织化学表达以及最高的SSTR2基因表达水平。在免疫组织化学和RT-qPCR研究中均观察到高级别脑膜瘤中有SSTR2缺失的趋势。约90%的培养犬脑膜瘤细胞显示SSTR2表达。在两种脑膜瘤细胞培养物中,通过蛋白质印迹法和RT-qPCR也检测到了SSTR2表达。本研究首次证明犬脑膜瘤表达SSTR2,且这种表达在体外得以维持。我们的结果虽然是初步的,但为进一步研究旨在寻找犬脑膜瘤的新型医学治疗策略,特别是针对无法手术切除的肿瘤提供了鼓励。

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