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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...

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Autores principales: Mannerström, Bettina, Kornilov, Roman, Abu-Shahba, Ahmed G., Chowdhury, Iftekhar M., Sinha, Snehadri, Seppänen-Kaijansinkko, Riitta, Kaur, Sippy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
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.
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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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