IOVS AJP: Regulatory, Integrative and Comparative Physiology
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(Investigative Ophthalmology and Visual Science. 2007;48:1219-1227.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0090
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Melanocortin 1 Receptor Is Expressed by Uveal Malignant Melanoma and Can Be Considered a New Target for Diagnosis and Immunotherapy

Mercedes N. López,1,2 Cristian Pereda,1 Marcos Ramírez,1 Ariadna Mendoza-Naranjo,1 Antonio Serrano,1 Arturo Ferreira,1 Rodrigo Poblete,3 Alexis M. Kalergis,4 Rolf Kiessling,5 and Flavio Salazar-Onfray1

1From the Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; 2Research Support Office, University of Chile Clinical Hospital, Santiago, Chile; 3Department of Ophthalmology, Hospital del Salvador, Santiago, Chile; 4Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontifica Universidad Católica de Chile, Santiago, Chile; and 5Department of Oncology and Pathology, Cancer Centre Karolinska, Stockholm, Sweden.

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.






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