López Mercedes N, Pereda Cristian, Ramírez Marcos, Mendoza-Naranjo Ariadna, Serrano Antonio, Ferreira Arturo, Poblete Rodrigo, Kalergis Alexis M, Kiessling Rolf, Salazar-Onfray Flavio
Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1219-27. doi: 10.1167/iovs.06-0090.
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.
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 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.
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.
葡萄膜黑色素瘤是成人中最常见的原发性恶性眼癌。与皮肤黑色素瘤相比，这种肿瘤具有独特的标志物表达模式。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，评估其在葡萄膜黑色素瘤上的表达很重要。
使用两种新型单克隆抗体（MP1.1C11和MP1.1B7）检测葡萄膜黑色素瘤中MC1R的表达。通过免疫组织化学分析从17名患者获得的组织样本中MC1R的表达。此外，用促炎细胞因子处理葡萄膜黑色素瘤细胞系，然后通过流式细胞术分析MC1R细胞表面表达。
结果表明，葡萄膜黑色素瘤中MC1R的表达程度明显高于其他黑色素瘤标志物。使用MP1.1C11或MP1.1B7，在95%的测试黑色素瘤组织中检测到MC1R，包括1例肝转移灶。相比之下，MART-1、S100特异性蛋白和gp-100分别仅在66%、33%和67%的分析样本中表达。结果还表明，尽管MC1R主要位于细胞内，但细胞因子如IFN-γ、TNF-α、IL-4和IL-10可促进其细胞表面表达。
这些观察结果支持将MC1R纳入葡萄膜黑色素瘤诊断标志物组。靶向细胞因子诱导的MC1R的MC1R特异性抗体的治疗应用可能需要靶分子在肿瘤细胞表面表达。此处提供的数据支持MC1R作为葡萄膜黑色素瘤的新标志物和推定治疗靶点。
