Extracellular Vesicles Derived from Metastatic Melanoma Cells Transfer α7-nAChR mRNA, Thus Increasing the Surface Expression of the Receptor and Stimulating the Growth of Normal Keratinocytes

Acta Naturae

article

Maksim L. Bychkov¹  Artem V. Kirichenko²  Irina N. Mikhaylova³  Alexander S. Paramonov¹  Mikhail P. Kirpichnikov⁴  Mikhail A. Shulepko¹  Ekatherine N. Lyukmanova⁴ 

[1] Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences;Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow Institute of Physics and Technology, State University;Federal State Budgetary Institution named N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Healthcare of the Russian Federation;Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Interdisciplinary Scientific and Educational School of Moscow University "Molecular Technologies of the Living Systems and Synthetic Biology", Lomonosov Moscow State University

关键词: α7-nAChR;    vesicles;    metastatic melanoma;    keratinocytes;    oncotherapy;    cancer.;   

DOI  :  10.32607/actanaturae.11734

学科分类：生物技术

来源: Moskovskii Gosudarstvennyi Universitet im.M.V.Lomonosova/M.V.Lomonosov Moscow State University

【 摘 要 】

We have previously shown that extracellular vesicles secreted by metastatic melanoma cells stimulate 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 α7-type nicotinic acetylcholine receptor (α7-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 α7-nAChR increased the surface expression of α7-nAChR in normal Het-1A keratinocytes and stimulated their growth. Meanwhile, both of these effects disappeared in the presence of α-bungarotoxin, an α7-nAChR inhibitor. A bioinformatic analysis revealed a correlation between the increased expression of the CHRNA7 gene coding α7-nAChR in patients with metastatic melanoma and a poor survival prognosis. Therefore, extracellular vesicles derived from metastatic melanoma cells can transfer mRNA coding α7-nAChR, thus enhancing the surface expression of this receptor and stimulating the growth of normal keratinocytes. Targeting of α7-nAChR may become a new strategy for controlling the malignant transformation of keratinocytes.

【 授权许可】

Unknown