Original Article
Subject Category: Melanocytes/Melanoma
Journal of Investigative Dermatology (2008) 128, 972–979. doi:10.1038/sj.jid.5701111; published online 1 November 2007
Expression of Ligands to NKp46 in Benign and Malignant Melanocytes
Emanuela Cagnano1,6, Oren Hershkovitz2,3,6, Alon Zilka2,3, Ahuva Bar-Ilan2,3, Alexandra Golder2,3, Netta Sion-Vardy1, Alexander Bogdanov-Berezovsky4, Ofer Mandelboim5, Daniel Benharroch1 and Angel Porgador2,3
- 1Department of Pathology, The Soroka University Medical Center, Beer-Sheva, Israel
- 2The Shraga Segal, Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- 3The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- 4Department of Plastic Surgery, The Soroka University Medical Center, Beer-Sheva, Israel
- 5The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Correspondence: Dr Angel Porgador, Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. E-mail: angel@bgu.ac.il
6These authors have contributed equally to this work.
Received 23 January 2007; Revised 18 June 2007; Accepted 15 August 2007; Published online 1 November 2007.
Abstract
Human melanoma cell lines were shown to express ligands for the natural cytotoxicity receptor, NKp46, expressed by natural killer (NK) cells. We aimed to examine the expression of ligands for NKp46 by various primary human melanocytic cells and melanocytic lesions. Sections from primary nevi and melanomas were tested for expression of NKp46 ligands employing chimeric NKp46-Fc for staining. The melanocytes present in the reticular dermis were negative for NKp46 ligands in common nevi; in malignant melanocytic lesions, the deeper melanocytes were focally positive. In dermoepidermal junction of all melanocytic lesions, the melanocytes showed enhanced expression of NKp46 ligands. Melanophages in all lesions were consistently positive for NKp46 ligands. These observations establish the expression of NKp46 ligands by primary-transformed melanocytes. Normal melanocytes did not express ligands to NKp46. Therefore, the results show (i) a correlation between the malignant potential of the lesion and the expression of NKp46 ligands in the reticular dermis, and (ii) enhanced expression of NKp46 ligands in the active proliferation zone (dermoepidermal junction) of nevi and melanomas. Ligands to NKp46 were expressed on the membrane and within the cells. The physiological role of NKp46 ligands in the progression of malignancy within melanocytic lesions should be explored further.
Abbreviations:
CN, compound nevi; DEJ, dermoepidermal junction; DysN, dysplastic nevi; IN, intradermal nevi; NCR, natural cytotoxicity receptor; NK, natural killer; NKp46D2, membrane-proximal domain of NKp46; SSMM, superficial spreading malignant melanoma
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