Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1784673962692706304 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8945455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT bychkovmaximl extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes AT kirichenkoartemv extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes AT mikhaylovairinan extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes AT paramonovalexanders extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes AT yastremskyevgenyv extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes AT kirpichnikovmikhailp extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes AT shulepkomikhaila extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes AT lyukmanovaekaterinan extracellularvesiclesderivedfromacidifiedmetastaticmelanomacellsstimulategrowthmigrationandstemnessofnormalkeratinocytes |