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Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles
Extracellular vesicles (EVs) are central to intercellular communication and play an important role in cancer progression and development. Osteosarcoma (OS) is an aggressive bone tumour, characterized by the presence of malignant mesenchymal cells. The specific tumour-driving genetic alterations that...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557543/ https://www.ncbi.nlm.nih.gov/pubmed/30907225 http://dx.doi.org/10.1080/15592294.2019.1585177 |
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author | Mannerström, Bettina Kornilov, Roman Abu-Shahba, Ahmed G. Chowdhury, Iftekhar M. Sinha, Snehadri Seppänen-Kaijansinkko, Riitta Kaur, Sippy |
author_facet | Mannerström, Bettina Kornilov, Roman Abu-Shahba, Ahmed G. Chowdhury, Iftekhar M. Sinha, Snehadri Seppänen-Kaijansinkko, Riitta Kaur, Sippy |
author_sort | Mannerström, Bettina |
collection | PubMed |
description | Extracellular vesicles (EVs) are central to intercellular communication and play an important role in cancer progression and development. Osteosarcoma (OS) is an aggressive bone tumour, characterized by the presence of malignant mesenchymal cells. The specific tumour-driving genetic alterations that are associated with OS development are currently poorly understood. Mesenchymal stem cells (MSCs) of osteogenic lineage have been postulated as likely candidates as the cells of origin for OS, thus indicating that MSCs and OS stroma cells may be related cell types. Therefore, this study set out to examine the EV-mediated intercellular crosstalk of MSCs and OS. MSCs and pre-osteoblasts were treated with OS-EVs at different time points, and the epigenetic signature of OS-EVs was assessed by methylation analysis of LINE-1 (long interspersed element) and tumour suppressor genes. In addition, surface markers and expression of specific genes were also evaluated. Our data indicated that OS-EVs mediated LINE-1 hypomethylation in MSCs, whereas an opposite effect was seen in pre-osteoblasts, indicating that MSCs but not pre-osteoblasts were susceptible to epigenetic transformation. Thus, OS-EVs modulated the fate of MSCs by modulating the epigenetic status, and also influenced the expression of genes related to bone microenvironment remodelling. Overall, this study provided evidence that epigenetic regulation appears to be an early event in the transformation of MSCs during the development of OS. Elucidating the mechanisms of EV-mediated communication may lead to new avenues for therapeutic exploitation. |
format | Online Article Text |
id | pubmed-6557543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-65575432019-06-19 Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles Mannerström, Bettina Kornilov, Roman Abu-Shahba, Ahmed G. Chowdhury, Iftekhar M. Sinha, Snehadri Seppänen-Kaijansinkko, Riitta Kaur, Sippy Epigenetics Research Paper Extracellular vesicles (EVs) are central to intercellular communication and play an important role in cancer progression and development. Osteosarcoma (OS) is an aggressive bone tumour, characterized by the presence of malignant mesenchymal cells. The specific tumour-driving genetic alterations that are associated with OS development are currently poorly understood. Mesenchymal stem cells (MSCs) of osteogenic lineage have been postulated as likely candidates as the cells of origin for OS, thus indicating that MSCs and OS stroma cells may be related cell types. Therefore, this study set out to examine the EV-mediated intercellular crosstalk of MSCs and OS. MSCs and pre-osteoblasts were treated with OS-EVs at different time points, and the epigenetic signature of OS-EVs was assessed by methylation analysis of LINE-1 (long interspersed element) and tumour suppressor genes. In addition, surface markers and expression of specific genes were also evaluated. Our data indicated that OS-EVs mediated LINE-1 hypomethylation in MSCs, whereas an opposite effect was seen in pre-osteoblasts, indicating that MSCs but not pre-osteoblasts were susceptible to epigenetic transformation. Thus, OS-EVs modulated the fate of MSCs by modulating the epigenetic status, and also influenced the expression of genes related to bone microenvironment remodelling. Overall, this study provided evidence that epigenetic regulation appears to be an early event in the transformation of MSCs during the development of OS. Elucidating the mechanisms of EV-mediated communication may lead to new avenues for therapeutic exploitation. Taylor & Francis 2019-03-24 /pmc/articles/PMC6557543/ /pubmed/30907225 http://dx.doi.org/10.1080/15592294.2019.1585177 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Research Paper Mannerström, Bettina Kornilov, Roman Abu-Shahba, Ahmed G. Chowdhury, Iftekhar M. Sinha, Snehadri Seppänen-Kaijansinkko, Riitta Kaur, Sippy Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles |
title | Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles |
title_full | Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles |
title_fullStr | Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles |
title_full_unstemmed | Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles |
title_short | Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles |
title_sort | epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557543/ https://www.ncbi.nlm.nih.gov/pubmed/30907225 http://dx.doi.org/10.1080/15592294.2019.1585177 |
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