Irisin and Metastatic Melanoma: Selective Anti-Invasiveness Activity in BRAF Wild-Type Cells.

Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBL, LND1, Hmel1 and M3) capable of the oncogenic activation of BRAF. We treated MM cells with different concentrations of r-irisin (10 nM, 25 nM, 50 nM, 100 nM) for 24 h-48 h. An MTT assay highlighted that r-irisin did not affect the proliferation of MM cells. We subsequently treated MM cells with 10 nM r-irisin, corresponding to the dose exhibiting biological activity in vitro. Irisin reduced the invasive ability of only LND1 ( < 0.05), which highly expressed αv gene levels, but did not affect the invasion of BRAF cells. Gelatin zymography analysis showed a reduction in the enzymatic activity of MMP-2 and MMP-9 in BRAF cells treated with 10 nM r-irisin. Moreover, gene expression analysis (qPCR) of and and of the fibrinolytic system (, and ) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAF. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells.