Histamine H4 Receptor Expression in Human Nevus and Melanoma

N MASSARI; VA MEDINA; D MARTINEL LAMAS; RM BERGOC; ES RIVERA

Sochi

Congreso; European Histamine Research Society, XL Annual Meeting; 2011

European Histamine Research Society

Human malignant melanoma is a highly metastatic cancer resistant to conventional therapy. Histamine acts as a growth factor in this neoplasm and it was reported the expression of the histamine H1, H2, and H3 receptors in melanoma cell lines. We have previously demonstrated the presence of histamine H4 receptor (H4R) in WM35 primary human melanoma cells and in M1/15 highly metastatic human melanoma cells. Histamine inhibits proliferation and migration, and induces differentiation and senescence through the activation of H4R. The aim of this work was to investigate the presence of H4R in nevus and in human melanoma biopsies and the association with proliferating cell nuclear antigen (PCNA), histamine levels and histidine decarboxilase (HDC) expression by immunohistochemistry. The immunohistochemical analysis showed that H4R was detected in 42% (8/19) of melanoma biopsies and in 83% (15/18) of nevus and higher levels of expression were observed (*p=0,0107, Mann Whitney’s two tail test).We additionally evaluated PCNA immunostaining as an indicator of active proliferation, and we observed that only melanomas expressed PCNA, which was inverse correlated with H4R expression (*p= 0,0158; Sperman r= - 0,54). Melanoma tissues expressed higher levels of HDC, but we didn`t observed any differences about histamine levels. The identification of H4R and the elucidation of its role in the development and growth of human malignant melanoma may represent an essential clue for advances in the treatment of this disease. Present findings suggest that H4R may be involved in the regulation of melanoma growth and progression, representing a novel molecular target for a new therapeutic approach.