| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-02-25 |
| タイトル |
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タイトル |
Bortezomib Reduces the Tumorigenicity of Multiple Myeloma via Downregulation of Upregulated Targets in Clonogenic Side Population Cells |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 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 |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 作成者 |
Nara, Miho
Teshima, Kazuaki
Watanabe, Atsushi
Ito, Mitsugu
Iwamoto, Keiko
Kitabayashi, Atsushi
Kume, Masaaki
Hatano, Yoshiaki
Takahashi, Naoto
Iida, Shinsuke
Sawada, Kenichi
Tagawa, Hiroyuki
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| 内容記述 |
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内容記述タイプ |
Abstract |
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内容記述 |
Side population (SP) cells in cancers, including multiple myeloma, exhibit tumor-initiating characteristics. In the present study, we isolated SP cells from human myeloma cell lines and primary tumors to detect potential therapeutic targets specifically expressed in SP cells. We found that SP cells from myeloma cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11) express CD138 and that non-SP cells include a CD138-negative population. Serial transplantation of SP and non-SP cells into NOD/Shi-scid IL-2 gamma nul mice revealed that clonogenic myeloma SP cells are highly tumorigenic and possess a capacity for self-renewal. Gene expression analysis showed that SP cells from five MM cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11, JJN3) express genes involved in the cell cycle and mitosis (e. g., CCNB1, CDC25C, CDC2, BIRC5, CENPE, SKA1, AURKB, KIFs, TOP2A, ASPM), polycomb (e. g., EZH2, EPC1) and ubiquitin-proteasome (e. g., UBE2D3, UBE3C, PSMA5) more strongly than do non-SP cells. Moreover, CCNB1, AURKB, EZH2 and PSMA5 were also upregulated in the SPs from eight primary myeloma samples. On that basis, we used an aurora kinase inhibitor (VX-680) and a proteasome inhibitor (bortezomib) with RPMI 8226 and AMO1 cells to determine whether these agents could be used to selectively target the myeloma SP. We found that both these drugs reduced the SP fraction, though bortezomib did so more effectively than VX-680 due to its ability to reduce levels of both phospho-histone H3 (p-hist. H3) and EZH2; VX-680 reduced only p-hist. H3. This is the first report to show that certain oncogenes are specifically expressed in the myeloma SP, and that bortezomib effectively downregulates expression of their products. Our approach may be useful for screening new agents with which to target a cell population possessing strong tumor initiating potential in multiple myeloma. |
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言語 |
en |
| 出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 書誌情報 |
en : PLOS ONE
巻 8,
号 3,
発行日 2013
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| 収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1932-6203 |
| 出版者 |
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出版者 |
Public Library of Science |
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言語 |
en |
| 関連情報 |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0056954 |
| 権利情報 |
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権利情報 |
© 2013 Nara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
iA_2022_129.pdf (1.1 MB)
