Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles

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Mannerström , B , Kornilov , R , Abu-Shahba , A G , Chowdhury , I M , Sinha , S , Seppänen-Kaijansinkko , R & Kaur , S 2019 , ' Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles ' , Epigenetics , vol. 14 , no. 4 , pp. 352-364 . https://doi.org/10.1080/15592294.2019.1585177

Title: Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles
Author: Mannerström, Bettina; Kornilov, Roman; Abu-Shahba, Ahmed G.; Chowdhury, Iftekhar M.; Sinha, Snehadri; Seppänen-Kaijansinkko, Riitta; Kaur, Sippy
Other contributor: University of Helsinki, Department of Oral and Maxillofacial Diseases
University of Helsinki, Department of Oral and Maxillofacial Diseases
University of Helsinki, Clinicum
University of Helsinki, Department of Oral and Maxillofacial Diseases
University of Helsinki, Department of Oral and Maxillofacial Diseases
University of Helsinki, Department of Oral and Maxillofacial Diseases
University of Helsinki, Department of Oral and Maxillofacial Diseases




Date: 2019-04-03
Language: eng
Number of pages: 13
Belongs to series: Epigenetics
ISSN: 1559-2294
DOI: https://doi.org/10.1080/15592294.2019.1585177
URI: http://hdl.handle.net/10138/306725
Abstract: 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.
Subject: Osteosarcoma
mesenchymal stem cells
osteogenesis
extracellular vesicles
LINE-1 methylation
DNA methylation
flow cytometry
CANCER PROGRESSION
MEDIATED TRANSFER
PROGENITOR-CELL
MICROVESICLES
EXOSOMES
HYPERMETHYLATION
MICROENVIRONMENT
HYPOMETHYLATION
PROTEINS
DNA
1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
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