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.
Bibliographical noteFunding Information:
This study was supported by grants from the Ministry of Health (MOH) and the Israel Cancer Research Foundation (ICRF). This work was also supported by the Cooperation Program of the Deutsches Krebsforschungszentrum (DKFZ) and Israel's Ministry of Science (MOS). We thank Ms Eugenia Mejinovsky for assistance in staining of the nevi and melanoma sections. We also thank Dr Robert A. Weinberg (MIT, Cambridge, MA) and Dr Riki Perlman (Hadassah Medical Center, Jerusalem, Israel) for the Mel-STR cells. We thank Dr Chaim Rubinovitz (Soroka Skin Bank) for technical assistance. This study was carried out in Ben-Gurion University, Beer-Sheva, Israel.