Autonomous histamine metabolism in human melanoma cells

Melanoma cells constitutively produce various cytokines as well as growth factors and express their corresponding receptors. Exogenous histamine is known to be a growth factor for some tumours while in other cases histamine inhibits tumour growth, and acts on G protein-coupled H1 and H2 histamine receptors. In previous studies we have detected the expression of the l-histidine decarboxylase (HDC) gene and the presence of HDC protein in human melanoma cell lines. In the present study, the activities of the histamine-forming enzyme HDC and of the degrading enzymes diamine oxidase (DAO) and histamine N-methyltransferase (HNMT) were measured in primary (WM35 and WM983) and metastatic (M1 and HT168) human melanoma cell lines. HDC activity was found in WM35 and WM983 cell lines, while detectable HNMT activity was measured in WM983, M1 and HT168 lines. In contrast, DAO showed very low activity in melanoma cell lines. Melanoma cells release a detectable amount of histamine into the medium without external stimuli. These findings support the possibility of autonomous histamine metabolism in melanoma cells. Our results suggest that not only exogenous histamine but also histamine produced and released by the melanoma cells and acting as an autocrine and paracrine factor may influence cell proliferation and modulate the in situ immune response of the host.