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生长抑素受体作为人眼葡萄膜黑色素瘤的分子靶点。

Somatostatin Receptors as Molecular Targets in Human Uveal Melanoma.

机构信息

Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.

Department of Pathology, University of Debrecen, 4032 Debrecen, Hungary.

出版信息

Molecules. 2018 Jun 26;23(7):1535. doi: 10.3390/molecules23071535.

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with an incidence of 4⁻5 cases per million. The prognosis of UM is very poor. In the present study, our aim was to investigate the expression of mRNA and protein for somatostatin receptor types-1, -2, -3, -4, -5 (SSTR-1⁻5) in human UM tissue samples and in OCM-1 and OCM-3 human UM cell lines by qRT-PCR, western blot and ligand competition assay. The mRNA for SSTR-2 showed markedly higher expression in UM tissues than SSTR-5. The presence of SSTRs was demonstrated in 70% of UM specimens using ligand competition assay and both human UM models displayed specific high affinity SSTRs. Among the five SSTRs, the mRNA investigated for SSTR-2 and SSTR-5 receptors was strongly expressed in both human UM cell lines, SSTR-5 showing the highest expression. The presence of the SSTR-2 and SSTR-5 receptor proteins was confirmed in both cell lines by western blot. In summary, the expression of somatostatin receptors in human UM specimens and in OCM-1 and OCM-3 human UM cell lines suggests that they could serve as a potential molecular target for therapy of UM using modern powerful cytotoxic SST analogs targeting SSTR-2 and SSTR-5 receptors.

摘要

葡萄膜黑色素瘤 (UM) 是成年人中最常见的原发性眼内恶性肿瘤,发病率为每百万 4⁻5 例。UM 的预后非常差。在本研究中,我们旨在通过 qRT-PCR、western blot 和配体竞争分析,研究 somatostatin 受体类型-1、-2、-3、-4、-5(SSTR-1⁻5)在人 UM 组织样本和 OCM-1 和 OCM-3 人 UM 细胞系中的 mRNA 和蛋白表达。与 SSTR-5 相比,SSTR-2 在 UM 组织中的 mRNA 表达明显更高。通过配体竞争分析,在 70%的 UM 标本中证实了 SSTRs 的存在,两种人 UM 模型均显示出特异性高亲和力 SSTRs。在这五个 SSTR 中,研究的 SSTR-2 和 SSTR-5 受体 mRNA 在两种人 UM 细胞系中均强烈表达,SSTR-5 表达最高。western blot 证实了两种细胞系中 SSTR-2 和 SSTR-5 受体蛋白的存在。总之,人 UM 标本和 OCM-1 和 OCM-3 人 UM 细胞系中 somatostatin 受体的表达表明,它们可能成为使用针对 SSTR-2 和 SSTR-5 受体的现代强大细胞毒性 SST 类似物治疗 UM 的潜在分子靶标。

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