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Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles

Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and auto...

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Autores principales: Hanelova, Klara, Raudenska, Martina, Kratochvilova, Monika, Navratil, Jiri, Vicar, Tomas, Bugajova, Maria, Gumulec, Jaromir, Masarik, Michal, Balvan, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10210466/
https://www.ncbi.nlm.nih.gov/pubmed/37226246
http://dx.doi.org/10.1186/s12964-023-01126-z
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author Hanelova, Klara
Raudenska, Martina
Kratochvilova, Monika
Navratil, Jiri
Vicar, Tomas
Bugajova, Maria
Gumulec, Jaromir
Masarik, Michal
Balvan, Jan
author_facet Hanelova, Klara
Raudenska, Martina
Kratochvilova, Monika
Navratil, Jiri
Vicar, Tomas
Bugajova, Maria
Gumulec, Jaromir
Masarik, Michal
Balvan, Jan
author_sort Hanelova, Klara
collection PubMed
description Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGFβ1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-α, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01126-z.
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spelling pubmed-102104662023-05-26 Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles Hanelova, Klara Raudenska, Martina Kratochvilova, Monika Navratil, Jiri Vicar, Tomas Bugajova, Maria Gumulec, Jaromir Masarik, Michal Balvan, Jan Cell Commun Signal Research Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGFβ1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-α, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01126-z. BioMed Central 2023-05-24 /pmc/articles/PMC10210466/ /pubmed/37226246 http://dx.doi.org/10.1186/s12964-023-01126-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hanelova, Klara
Raudenska, Martina
Kratochvilova, Monika
Navratil, Jiri
Vicar, Tomas
Bugajova, Maria
Gumulec, Jaromir
Masarik, Michal
Balvan, Jan
Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
title Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
title_full Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
title_fullStr Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
title_full_unstemmed Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
title_short Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
title_sort autophagy modulators influence the content of important signalling molecules in ps-positive extracellular vesicles
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10210466/
https://www.ncbi.nlm.nih.gov/pubmed/37226246
http://dx.doi.org/10.1186/s12964-023-01126-z
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