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Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes

Sphingolipids (SLs), glycosphingolipids (GSLs), and eicosanoids are bioactive lipids, which play important roles in the etiology of various diseases, including cancer. However, their content and roles in cancer cells, and in particular in the exosomes derived from tumor cells, remain insufficiently...

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Autores principales: Machala, Miroslav, Slavík, Josef, Kováč, Ondrej, Procházková, Jiřina, Pěnčíková, Kateřina, Pařenicová, Martina, Straková, Nicol, Kotouček, Jan, Kulich, Pavel, Mollerup, Steen, Vondráček, Jan, Hýžďalová, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431443/
https://www.ncbi.nlm.nih.gov/pubmed/34502101
http://dx.doi.org/10.3390/ijms22179195
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author Machala, Miroslav
Slavík, Josef
Kováč, Ondrej
Procházková, Jiřina
Pěnčíková, Kateřina
Pařenicová, Martina
Straková, Nicol
Kotouček, Jan
Kulich, Pavel
Mollerup, Steen
Vondráček, Jan
Hýžďalová, Martina
author_facet Machala, Miroslav
Slavík, Josef
Kováč, Ondrej
Procházková, Jiřina
Pěnčíková, Kateřina
Pařenicová, Martina
Straková, Nicol
Kotouček, Jan
Kulich, Pavel
Mollerup, Steen
Vondráček, Jan
Hýžďalová, Martina
author_sort Machala, Miroslav
collection PubMed
description Sphingolipids (SLs), glycosphingolipids (GSLs), and eicosanoids are bioactive lipids, which play important roles in the etiology of various diseases, including cancer. However, their content and roles in cancer cells, and in particular in the exosomes derived from tumor cells, remain insufficiently characterized. In this study, we evaluated alterations of SL and GSL levels in transformed cells and their exosomes, using comparative HPLC-MS/MS analysis of parental human bronchial epithelial cells HBEC-12KT and their derivative, benzo[a]pyrene-transformed HBEC-12KT-B1 cells with the acquired mesenchymal phenotype. We examined in parallel SL/GSL contents in the exosomes released from both cell lines. We found significant alterations of the SL/GSL profile in the transformed cell line, which corresponded well with alterations of the SL/GSL profile in exosomes derived from these cells. This suggested that a majority of SLs and GSLs were transported by exosomes in the same relative pattern as in the cells of origin. The only exceptions included decreased contents of sphingosin, sphingosin-1-phosphate, and lactosylceramide in exosomes derived from the transformed cells, as compared with the exosomes derived from the parental cell line. Importantly, we found increased levels of ceramide phosphate, globoside Gb3, and ganglioside GD3 in the exosomes derived from the transformed cells. These positive modulators of epithelial–mesenchymal transition and other pro-carcinogenic processes might thus also contribute to cancer progression in recipient cells. In addition, the transformed HBEC-12KT-B1 cells also produced increased amounts of eicosanoids, in particular prostaglandin E2. Taken together, the exosomes derived from the transformed cells with specifically upregulated SL and GSL species, and increased levels of eicosanoids, might contribute to changes within the cancer microenvironment and in recipient cells, which could in turn participate in cancer development. Future studies should address specific roles of individual SL and GSL species identified in the present study.
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spelling pubmed-84314432021-09-11 Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes Machala, Miroslav Slavík, Josef Kováč, Ondrej Procházková, Jiřina Pěnčíková, Kateřina Pařenicová, Martina Straková, Nicol Kotouček, Jan Kulich, Pavel Mollerup, Steen Vondráček, Jan Hýžďalová, Martina Int J Mol Sci Article Sphingolipids (SLs), glycosphingolipids (GSLs), and eicosanoids are bioactive lipids, which play important roles in the etiology of various diseases, including cancer. However, their content and roles in cancer cells, and in particular in the exosomes derived from tumor cells, remain insufficiently characterized. In this study, we evaluated alterations of SL and GSL levels in transformed cells and their exosomes, using comparative HPLC-MS/MS analysis of parental human bronchial epithelial cells HBEC-12KT and their derivative, benzo[a]pyrene-transformed HBEC-12KT-B1 cells with the acquired mesenchymal phenotype. We examined in parallel SL/GSL contents in the exosomes released from both cell lines. We found significant alterations of the SL/GSL profile in the transformed cell line, which corresponded well with alterations of the SL/GSL profile in exosomes derived from these cells. This suggested that a majority of SLs and GSLs were transported by exosomes in the same relative pattern as in the cells of origin. The only exceptions included decreased contents of sphingosin, sphingosin-1-phosphate, and lactosylceramide in exosomes derived from the transformed cells, as compared with the exosomes derived from the parental cell line. Importantly, we found increased levels of ceramide phosphate, globoside Gb3, and ganglioside GD3 in the exosomes derived from the transformed cells. These positive modulators of epithelial–mesenchymal transition and other pro-carcinogenic processes might thus also contribute to cancer progression in recipient cells. In addition, the transformed HBEC-12KT-B1 cells also produced increased amounts of eicosanoids, in particular prostaglandin E2. Taken together, the exosomes derived from the transformed cells with specifically upregulated SL and GSL species, and increased levels of eicosanoids, might contribute to changes within the cancer microenvironment and in recipient cells, which could in turn participate in cancer development. Future studies should address specific roles of individual SL and GSL species identified in the present study. MDPI 2021-08-25 /pmc/articles/PMC8431443/ /pubmed/34502101 http://dx.doi.org/10.3390/ijms22179195 Text en © 2021 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
Machala, Miroslav
Slavík, Josef
Kováč, Ondrej
Procházková, Jiřina
Pěnčíková, Kateřina
Pařenicová, Martina
Straková, Nicol
Kotouček, Jan
Kulich, Pavel
Mollerup, Steen
Vondráček, Jan
Hýžďalová, Martina
Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes
title Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes
title_full Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes
title_fullStr Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes
title_full_unstemmed Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes
title_short Changes in Sphingolipid Profile of Benzo[a]pyrene-Transformed Human Bronchial Epithelial Cells Are Reflected in the Altered Composition of Sphingolipids in Their Exosomes
title_sort changes in sphingolipid profile of benzo[a]pyrene-transformed human bronchial epithelial cells are reflected in the altered composition of sphingolipids in their exosomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431443/
https://www.ncbi.nlm.nih.gov/pubmed/34502101
http://dx.doi.org/10.3390/ijms22179195
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