Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance

Hida, Kyoko; Maishi, Nako; Akiyama, Kosuke et al.

Cancer science, 2017, 108(11), 2195-2203

Permalink : https://hdl.handle.net/2115/67988

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論文情報

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アクセス権
open access
URI
https://hdl.handle.net/2115/67988
タイトル
Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance
著者
Hida, Kyoko ; Maishi, Nako ; Akiyama, Kosuke ; Ohmura-Kakutani, Hitomi ; Torii, Chisaho ; Ohga, Noritaka ; Osawa, Takahiro ; Kikuchi, Hiroshi ; Morimoto, Hirofumi ; Morimoto, Masahiro ; Shindoh, Masanobu ; Shinohara, Nobuo ; Hida, Yasuhiro
e-Rad_Researcher
40399952
著者名
Hida, Kyoko
e-Rad_Researcher
00632423
著者名
Maishi, Nako
e-Rad_Researcher
10609100
著者名
Akiyama, Kosuke
著者名
Ohmura-Kakutani, Hitomi
著者名
Torii, Chisaho
e-Rad_Researcher
40548202
著者名
Ohga, Noritaka
著者名
Osawa, Takahiro
著者名
Kikuchi, Hiroshi
著者名
Morimoto, Hirofumi
著者名
Morimoto, Masahiro
e-Rad_Researcher
20162802
著者名
Shindoh, Masanobu
e-Rad_Researcher
90250422
著者名
Shinohara, Nobuo
e-Rad_Researcher
30399919
著者名
Hida, Yasuhiro
言語
英語
キーワード
Aldehyde dehydrogenase (ALDH)
angiogenesis
endothelial cell
resistance
tumor
発行日
2017-11
出版者
John Wiley & Sons
収録物名
Cancer science
巻(号)
108(11)
ページ
2195-2203
抄録
Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TEC) exhibit several altered phenotypes compared with normal endothelial cells (NEC). For example, TEC have chromosomal abnormalities and are resistant to several anticancer drugs. Furthermore, TEC contain stem cell-like populations with high aldehyde dehydrogenase (ALDH) activity (ALDHhigh TEC). ALDHhigh TEC have proangiogenic properties compared with ALDHlow TEC. However, the association between ALDHhigh TEC and drug resistance remains unclear. In the present study, we found that ALDH mRNA expression and activity were higher in both human and mouse TEC than in NEC. Human NEC:human microvascular endothelial cells (HMVEC) were treated with tumor-conditioned medium (tumor CM). The ALDHhigh population increased along with upregulation of stem-related genes such as multidrug resistance 1, CD90, ALP, and Oct-4. Tumor CM also induced sphere-forming ability in HMVEC. Platelet-derived growth factor (PDGF)-A in tumor CM was shown to induce ALDH expression in HMVEC. Finally, ALDHhigh TEC were resistant to fluorouracil (5-FU) in vitro and in vivo. ALDHhigh TEC showed a higher grade of aneuploidy compared with that in ALDHlow TEC. These results suggested that tumor-secreting factor increases ALDHhigh TEC populations that are resistant to 5-FU. Therefore, ALDHhigh TEC in tumor blood vessels might be an important target to overcome or prevent drug resistance.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution-NonCommercial 4.0 International
PISSN
1349-7006
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1111/cas.13388