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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-04-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2019.1585177 |
| _version_ | 1797678860929597440 |
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| author | Bettina Mannerström Roman Kornilov Ahmed G. Abu-Shahba Iftekhar M. Chowdhury Snehadri Sinha Riitta Seppänen-Kaijansinkko Sippy Kaur |
| author_facet | Bettina Mannerström Roman Kornilov Ahmed G. Abu-Shahba Iftekhar M. Chowdhury Snehadri Sinha Riitta Seppänen-Kaijansinkko Sippy Kaur |
| author_sort | Bettina Mannerström |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T23:06:04Z |
| format | Article |
| id | doaj.art-001186f455f7473b991cfef9fd1e750c |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:04Z |
| publishDate | 2019-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-001186f455f7473b991cfef9fd1e750c2023-09-21T13:09:21ZengTaylor & Francis GroupEpigenetics1559-22941559-23082019-04-0114435236410.1080/15592294.2019.15851771585177Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesiclesBettina Mannerström0Roman Kornilov1Ahmed G. Abu-Shahba2Iftekhar M. Chowdhury3Snehadri Sinha4Riitta Seppänen-Kaijansinkko5Sippy Kaur6University of Helsinki and Helsinki University HospitalUniversity of Helsinki and Helsinki University HospitalUniversity of Helsinki and Helsinki University HospitalUniversity of Helsinki and Helsinki University HospitalUniversity of Helsinki and Helsinki University HospitalUniversity of Helsinki and Helsinki University HospitalUniversity of Helsinki and Helsinki University HospitalExtracellular 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.http://dx.doi.org/10.1080/15592294.2019.1585177osteosarcomamesenchymal stem cellsosteogenesisextracellular vesiclesline-1 methylationdna methylationflow cytometry |
| spellingShingle | Bettina Mannerström Roman Kornilov Ahmed G. Abu-Shahba Iftekhar M. Chowdhury Snehadri Sinha Riitta Seppänen-Kaijansinkko Sippy Kaur Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles Epigenetics osteosarcoma mesenchymal stem cells osteogenesis extracellular vesicles line-1 methylation dna methylation flow cytometry |
| 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 | osteosarcoma mesenchymal stem cells osteogenesis extracellular vesicles line-1 methylation dna methylation flow cytometry |
| url | http://dx.doi.org/10.1080/15592294.2019.1585177 |
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