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Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes

Metastatic melanoma is a highly malignant tumor. Melanoma cells release extracellular vesicles (EVs), which contribute to the growth, metastasis, and malignancy of neighboring cells by transfer of tumor-promoting miRNAs, mRNA, and proteins. Melanoma microenvironment acidification promotes tumor prog...

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Autores principales: Bychkov, Maxim L., Kirichenko, Artem V., Mikhaylova, Irina N., Paramonov, Alexander S., Yastremsky, Evgeny V., Kirpichnikov, Mikhail P., Shulepko, Mikhail A., Lyukmanova, Ekaterina N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945455/
https://www.ncbi.nlm.nih.gov/pubmed/35327461
http://dx.doi.org/10.3390/biomedicines10030660
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author Bychkov, Maxim L.
Kirichenko, Artem V.
Mikhaylova, Irina N.
Paramonov, Alexander S.
Yastremsky, Evgeny V.
Kirpichnikov, Mikhail P.
Shulepko, Mikhail A.
Lyukmanova, Ekaterina N.
author_facet Bychkov, Maxim L.
Kirichenko, Artem V.
Mikhaylova, Irina N.
Paramonov, Alexander S.
Yastremsky, Evgeny V.
Kirpichnikov, Mikhail P.
Shulepko, Mikhail A.
Lyukmanova, Ekaterina N.
author_sort Bychkov, Maxim L.
collection PubMed
description Metastatic melanoma is a highly malignant tumor. Melanoma cells release extracellular vesicles (EVs), which contribute to the growth, metastasis, and malignancy of neighboring cells by transfer of tumor-promoting miRNAs, mRNA, and proteins. Melanoma microenvironment acidification promotes tumor progression and determines EVs’ properties. We studied the influence of EVs derived from metastatic melanoma cells cultivated at acidic (6.5) and normal (7.4) pH on the morphology and homeostasis of normal keratinocytes. Acidification of metastatic melanoma environment made EVs more prooncogenic with increased expression of prooncogenic mi221 RNA, stemless factor CD133, and pro-migration factor SNAI1, as well as with downregulated antitumor mir7 RNA. Incubation with EVs stimulated growth and migration both of metastatic melanoma cells and keratinocytes and changed the morphology of keratinocytes to stem-like phenotype, which was confirmed by increased expression of the stemness factors KLF and CD133. Activation of the AKT/mTOR and ERK signaling pathways and increased expression of epidermal growth factor receptor EGFR and SNAI1 were detected in keratinocytes upon incubation with EVs. Moreover, EVs reduced the production of different cytokines (IL6, IL10, and IL12) and adhesion factors (sICAM-1, sICAM-3, sPecam-1, and sCD40L) usually secreted by keratinocytes to control melanoma progression. Bioinformatic analysis revealed the correlation between decreased expression of these secreted factors and worse survival prognosis for patients with metastatic melanoma. Altogether, our data mean that metastatic melanoma EVs are important players in the transformation of normal keratinocytes.
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spelling pubmed-89454552022-03-25 Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes Bychkov, Maxim L. Kirichenko, Artem V. Mikhaylova, Irina N. Paramonov, Alexander S. Yastremsky, Evgeny V. Kirpichnikov, Mikhail P. Shulepko, Mikhail A. Lyukmanova, Ekaterina N. Biomedicines Article Metastatic melanoma is a highly malignant tumor. Melanoma cells release extracellular vesicles (EVs), which contribute to the growth, metastasis, and malignancy of neighboring cells by transfer of tumor-promoting miRNAs, mRNA, and proteins. Melanoma microenvironment acidification promotes tumor progression and determines EVs’ properties. We studied the influence of EVs derived from metastatic melanoma cells cultivated at acidic (6.5) and normal (7.4) pH on the morphology and homeostasis of normal keratinocytes. Acidification of metastatic melanoma environment made EVs more prooncogenic with increased expression of prooncogenic mi221 RNA, stemless factor CD133, and pro-migration factor SNAI1, as well as with downregulated antitumor mir7 RNA. Incubation with EVs stimulated growth and migration both of metastatic melanoma cells and keratinocytes and changed the morphology of keratinocytes to stem-like phenotype, which was confirmed by increased expression of the stemness factors KLF and CD133. Activation of the AKT/mTOR and ERK signaling pathways and increased expression of epidermal growth factor receptor EGFR and SNAI1 were detected in keratinocytes upon incubation with EVs. Moreover, EVs reduced the production of different cytokines (IL6, IL10, and IL12) and adhesion factors (sICAM-1, sICAM-3, sPecam-1, and sCD40L) usually secreted by keratinocytes to control melanoma progression. Bioinformatic analysis revealed the correlation between decreased expression of these secreted factors and worse survival prognosis for patients with metastatic melanoma. Altogether, our data mean that metastatic melanoma EVs are important players in the transformation of normal keratinocytes. MDPI 2022-03-12 /pmc/articles/PMC8945455/ /pubmed/35327461 http://dx.doi.org/10.3390/biomedicines10030660 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bychkov, Maxim L.
Kirichenko, Artem V.
Mikhaylova, Irina N.
Paramonov, Alexander S.
Yastremsky, Evgeny V.
Kirpichnikov, Mikhail P.
Shulepko, Mikhail A.
Lyukmanova, Ekaterina N.
Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes
title Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes
title_full Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes
title_fullStr Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes
title_full_unstemmed Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes
title_short Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes
title_sort extracellular vesicles derived from acidified metastatic melanoma cells stimulate growth, migration, and stemness of normal keratinocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945455/
https://www.ncbi.nlm.nih.gov/pubmed/35327461
http://dx.doi.org/10.3390/biomedicines10030660
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