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Title	en Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance
Creator	en Hida, Kyoko NRID 1000040399952 en Maishi, Nako NRID 1000000632423 en Akiyama, Kosuke NRID 1000010609100 en Ohmura-Kakutani, Hitomi en Torii, Chisaho en Ohga, Noritaka NRID 1000040548202 en Osawa, Takahiro en Kikuchi, Hiroshi en Morimoto, Hirofumi en Morimoto, Masahiro en Shindoh, Masanobu NRID 1000020162802 en Shinohara, Nobuo NRID 1000090250422 en Hida, Yasuhiro NRID 1000030399919
Accessrights	open access
Rights	http://creativecommons.org/licenses/by-nc/4.0/ en Creative Commons Attribution-NonCommercial 4.0 International
Subject	Other en Aldehyde dehydrogenase (ALDH) Other en angiogenesis Other en endothelial cell Other en resistance Other en tumor NDC 490
Description	Abstract en 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.
Publisher	en John Wiley & Sons
Date	Issued2017-11
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/67988
Relation	isIdenticalTo DOI https://doi.org/10.1111/cas.13388
Journal	PISSN 1349-7006 en Cancer science Volume Number108 Issue Number11 Page Start2195 Page End2203
File	fulltext Hida_et_al-2017-Cancer_Science.pdf 1.41 MB (application/pdf) Issued2017-11 fulltext cas13388-sup-0001-FigS1.tif 12.33 MB (image/tiff) Issued2017-11
Oaidate	2023-07-26