| Item type |
文献 / Documents(1) |
| 公開日 |
2021-03-23 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
|
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|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1038/s41375-019-0493-x |
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|
言語 |
ja |
|
|
関連名称 |
10.1038/s41375-019-0493-x |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling |
|
言語 |
en |
| 著者 |
Ho, Matthew
Chen, Tianzeng
Liu, Jiye
Dowling, Paul
ヒデシマ, テル
Zhang, Li
Morelli, Eugenio
Camci-Unal, Gulden
Wu, Xinchen
Tai, Yu-Tzu
Wen, Kenneth
Samur, Mehmet
Schlossman, Robert L.
Mazitschek, Ralph
Kavanagh, Emma L.
Lindsay, Sinéad
原田, 武志
McCann, Amanda
Anderson, Kenneth C.
O’Gorman, Peter
Bianchi, Giada
|
| 抄録 |
|
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内容記述タイプ |
Abstract |
|
内容記述 |
Multiple myeloma (MM) is an incurable cancer that derives pro-survival/proliferative signals from the bone marrow (BM) niche. Novel agents targeting not only cancer cells, but also the BM-niche have shown the greatest activity in MM. Histone deacetylases (HDACs) are therapeutic targets in MM and we previously showed that HDAC3 inhibition decreases MM proliferation both alone and in co-culture with bone marrow stromal cells (BMSC). In this study, we investigate the effects of HDAC3 targeting in BMSCs. Using both BMSC lines as well as patient-derived BMSCs, we show that HDAC3 expression in BMSCs can be induced by co-culture with MM cells. Knock-out (KO), knock-down (KD), and pharmacologic inhibition of HDAC3 in BMSCs results in decreased MM cell proliferation; including in autologous cultures of patient MM cells with BMSCs. We identified both quantitative and qualitative changes in exosomes and exosomal miRNA, as well as inhibition of IL-6 trans-signaling, as molecular mechanisms mediating anti-MM activity. Furthermore, we show that HDAC3-KD in BM endothelial cells decreases neoangiogenesis, consistent with a broad effect of HDAC3 targeting in the BM-niche. Our results therefore support the clinical development of HDAC3 inhibitors based not only on their direct anti-MM effects, but also their modulation of the BM microenvironment. |
|
言語 |
en |
| 書誌情報 |
en : Leukemia
巻 34,
号 1,
p. 196-209,
発行日 2019-05-29
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
08876924 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
14765551 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA10668706 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12305962 |
| 出版者 |
|
|
出版者 |
Springer Nature |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| EID |
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|
識別子 |
364705 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
leukem_34_1_196.pdf (4.2 MB)
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