Melanocortin 1 receptor is expressed by uveal malignant melanoma and can be considered a new target for diagnosis and immunotherapy.

Melanocortin 1 receptor is expressed by uveal malignant melanoma and can be considered a new target for diagnosis and immunotherapy.
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黑皮质素1受体由葡萄膜恶性黑色素瘤表达,可被认为是诊断和免疫治疗的新靶点。

DOI:
10.1167/iovs.06-0090
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发表时间:
2007
影响因子:
4.4
通讯作者:
F. Salazar
F. Salazar
中科院分区:
医学2区
文献类型:
--
作者:
Mercedes N López;C. Pereda;M. Ramírez;A. Mendoza‐Naranjo;A. Serrano;Arturo Ferreira;R. Poblete;A. Kalergis;R. Kiessling;F. Salazar

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目的 葡萄膜黑色素瘤是成人最常见的原发恶性眼癌。与皮肤黑色素瘤相比,该肿瘤具有不同的标志物表达模式。MC1R作为抗肿瘤免疫的潜在靶点正在研究中。由于MC1R具有潜在的免疫原性,因此评估其在葡萄膜黑色素瘤中的表达具有重要意义。 方法 应用两种新的单抗(MP1.1C11和MP1.1B7)检测葡萄膜黑色素瘤中MC1R的表达。采用免疫组织化学方法检测17例乳腺癌组织标本中MC1R的表达。此外,用促炎症细胞因子处理葡萄膜黑色素瘤细胞系,用流式细胞仪分析MC1R细胞表面的表达。 结果 结果表明,葡萄膜黑色素瘤表达MC1R的程度明显高于其他黑色素瘤标志物。使用MP1.1C11或MP1.1B7在95%的黑色素瘤组织中检测到MC1R,包括一例肝转移瘤。相比之下,MART-1、S100特异性蛋白和GP-100的表达分别仅占分析样本的66%、33%和67%。结果还表明,尽管MC1R主要定位于细胞内,但其细胞表面的表达可被细胞因子如干扰素-γ、肿瘤坏死因子-α、IL-4和IL-10所促进。 结论 这些观察结果支持将MC1R纳入葡萄膜黑色素瘤诊断标记物小组。针对细胞因子诱导的MC1R的MC1R特异性抗体的治疗应用可能需要在肿瘤细胞表面表达靶分子。本文提供的数据支持MC1R作为一种新的标记物和葡萄膜黑色素瘤的假定治疗靶点。
PURPOSE Uveal melanoma is the most common primary malignant ocular cancer in adults. This tumor has a distinct expression pattern of markers compared with cutaneous melanoma. MC1R is under study as a potential target for antitumor immunity. Because of the potential immunogenicity of MC1R, it is important to evaluate its expression on uveal melanomas. METHODS Two novel monoclonal antibodies (MP1.1C11 and MP1.1B7) were used to examine the expression of MC1R in uveal melanomas. Tissue samples obtained from 17 patients were analyzed for expression of MC1R by immunohistochemistry. Additionally, uveal melanoma cell lines were treated with proinflammatory cytokines, after which MC1R cell surface expression was analyzed by flow cytometry. RESULTS Results demonstrated that MC1R is expressed by uveal melanoma to a significantly greater extent than other melanoma markers. With the use of MP1.1C11 or MP1.1B7, MC1R was detected in 95% of the tested melanoma tissues, including one liver metastasis. In contrast, MART-1, S100-specific protein, and gp-100 were only expressed by 66%, 33%, and 67% of the analyzed samples, respectively. Results also demonstrated that even though MC1R is mainly located intracellularly, its cell surface expression can be promoted by cytokines such as IFN-gamma, TNF-alpha, IL-4, and IL-10. CONCLUSIONS These observations support the inclusion of MC1R in the panel of markers for the diagnosis of uveal melanoma. Therapeutic use of MC1R-specific antibodies targeting cytokine-induced MC1R potentially requires expression of the target molecule on the surfaces of tumor cells. Data presented here support MC1R as a new marker and a putative therapeutic target for uveal melanoma.
DOI: 10.1056/nejm199506153322402
发表时间: 1995-06-15
影响因子: 158.5
作者:
KEY, LL;RODRIGUIZ, RM;RIES, WL
通讯作者: RIES, WL
DOI: 10.1016/s0021-9258(18)82452-8
发表时间: 1993-07
期刊: The Journal of biological chemistry
影响因子: --
作者:
I. Gantz;Hiroto Miwa;Y. Konda;Y. Shimoto;T. Tashiro;S. Watson;J. Delvalle;Tadataka Yamada
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DOI: 10.1200/jco.2005.00.240
发表时间: 2005-04-01
影响因子: 45.3
作者:
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者: Rosenberg, SA
葡萄膜和皮肤黑色素瘤之间的免疫表型差异。
DOI: 10.1001/archopht.120.4.466
发表时间: 2002
期刊: Archives of ophthalmology (Chicago, Ill. : 1960)
影响因子: --
作者:
Iwamoto,Satori;Burrows,RobertC;Kalina,RobertE;George,David;Boehm,Michael;Bothwell,MarkA;Schmidt,Rodney
通讯作者: Schmidt,Rodney