Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-023-01126-z |
| _version_ | 1797817867135090688 |
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| author | Klara Hanelova Martina Raudenska Monika Kratochvilova Jiri Navratil Tomas Vicar Maria Bugajova Jaromir Gumulec Michal Masarik Jan Balvan |
| author_facet | Klara Hanelova Martina Raudenska Monika Kratochvilova Jiri Navratil Tomas Vicar Maria Bugajova Jaromir Gumulec Michal Masarik Jan Balvan |
| author_sort | Klara Hanelova |
| collection | DOAJ |
| description | Abstract 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. Video Abstract |
| first_indexed | 2024-03-13T08:59:46Z |
| format | Article |
| id | doaj.art-bdbb8751781d4a59816dd149d90fb378 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-13T08:59:46Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-bdbb8751781d4a59816dd149d90fb3782023-05-28T11:23:05ZengBMCCell Communication and Signaling1478-811X2023-05-0121112110.1186/s12964-023-01126-zAutophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesiclesKlara Hanelova0Martina Raudenska1Monika Kratochvilova2Jiri Navratil3Tomas Vicar4Maria Bugajova5Jaromir Gumulec6Michal Masarik7Jan Balvan8Department of Pathological Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Pathological Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Pathological Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Pathological Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Pathological Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Pathological Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Pathological Physiology, Faculty of Medicine, Masaryk UniversityDepartment of Pathological Physiology, Faculty of Medicine, Masaryk UniversityAbstract 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. Video Abstracthttps://doi.org/10.1186/s12964-023-01126-zExtracellular vesiclesPhosphatidylserine-positive extracellular vesiclesAutophagyAutophagy modulationHead and neck cancerProteomics |
| spellingShingle | Klara Hanelova Martina Raudenska Monika Kratochvilova Jiri Navratil Tomas Vicar Maria Bugajova Jaromir Gumulec Michal Masarik Jan Balvan Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles Cell Communication and Signaling Extracellular vesicles Phosphatidylserine-positive extracellular vesicles Autophagy Autophagy modulation Head and neck cancer Proteomics |
| 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 | Extracellular vesicles Phosphatidylserine-positive extracellular vesicles Autophagy Autophagy modulation Head and neck cancer Proteomics |
| url | https://doi.org/10.1186/s12964-023-01126-z |
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