Extracellular Vesicles Derived from Metastatic Melanoma Cells Transfer alpha 7-nAChR mRNA, Thus Increasing the Surface Expression of the Receptor and Stimulating the Growth of Normal Keratinocytes

We have previously shown that extracellular vesicles secreted by metastatic melanoma cells stim-ulate the growth, migration, and stemness of normal keratinocytes. This study showed for the first time that extracellular vesicles secreted by the metastatic melanoma cell lines mel H, mel Kor, and mel P contain, both at the mRNA and protein levels, the alpha 7-type nicotinic acetylcholine receptor (alpha 7-nAChR), which is involved in the regulation of the oncogenic signaling pathways in epithelial cells. Incubation with the vesicles secreted by mel H cells and containing the highest amount of mRNA coding alpha 7-nAChR increased the surface expres-sion of alpha 7-nAChR in normal Het-1A keratinocytes and stimulated their growth. Meanwhile, both of these effects disappeared in the presence of alpha-bungarotoxin, an alpha 7-nAChR inhibitor. A bioinformatic analysis re-vealed a correlation between the increased expression of the CHRNA7 gene coding alpha 7-nAChR in patients with metastatic melanoma and a poor survival prognosis. Therefore, extracellular vesicles derived from met-astatic melanoma cells can transfer mRNA coding alpha 7-nAChR, thus enhancing the surface expression of this receptor and stimulating the growth of normal keratinocytes. Targeting of alpha 7-nAChR may become a new for the transformation of keratinocytes.