Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype

Ohmura-Kakutani, Hitomi; Akiyama, Kosuke; Maishi, Nako; Ohga, Noritaka; Hida, Yasuhiro; Kawamoto, Taisuke; Iida, Junichiro; Shindoh, Masanobu; Tsuchiya, Kunihiko; Shinohara, Nobuo; Hida, Kyoko

Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype

Ohmura-Kakutani, Hitomi; Akiyama, Kosuke; Maishi, Nako et al.

PLOS one, 2014, 9(12), e113910

Permalink : https://hdl.handle.net/2115/57970

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アクセス権	open access
URI	https://hdl.handle.net/2115/57970
タイトル	Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype
著者	Ohmura-Kakutani, Hitomi ; Akiyama, Kosuke ; Maishi, Nako ; Ohga, Noritaka ; Hida, Yasuhiro ; Kawamoto, Taisuke ; Iida, Junichiro ; Shindoh, Masanobu ; Tsuchiya, Kunihiko ; Shinohara, Nobuo ; Hida, Kyoko
著者名 Ohmura-Kakutani, Hitomi
e-Rad_Researcher 10609100 著者名 Akiyama, Kosuke
e-Rad_Researcher 00632423 著者名 Maishi, Nako
e-Rad_Researcher 40548202 著者名 Ohga, Noritaka
e-Rad_Researcher 30399919 著者名 Hida, Yasuhiro
著者名 Kawamoto, Taisuke
e-Rad_Researcher 90151232 著者名 Iida, Junichiro
e-Rad_Researcher 20162802 著者名 Shindoh, Masanobu
著者名 Tsuchiya, Kunihiko
e-Rad_Researcher 90250422 著者名 Shinohara, Nobuo
e-Rad_Researcher 40399952 著者名 Hida, Kyoko
言語	英語
発行日	2014-12-01
出版者	Public Library of Science
収録物名	PLOS one
巻(号)	9(12)
ページ	e113910
抄録	Tumor blood vessels play an important role in tumor progression and metastasis. It has been reported that tumor endothelial cells (TECs) exhibit highly angiogenic phenotypes compared with those of normal endothelial cells (NECs). TECs show higher proliferative and migratory abilities than those NECs, together with upregulation of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2). Furthermore, compared with NECs, stem cell markers such as Sca-1, CD90, and multidrug resistance 1 are upregulated in TECs, suggesting that stem-like cells exist in tumor blood vessels. In this study, to reveal the biological role of stem-like TECs, we analyzed expression of the stem cell marker aldehyde dehydrogenase (ALDH) in TECs and characterized ALDH(high) TECs. TECs and NECs were isolated from melanoma-xenografted nude mice and normal dermis, respectively. ALDH mRNA expression and activity were higher in TECs than those in NECs. Next, ALDH(high/low) TECs were isolated by fluorescence-activated cell sorting to compare their characteristics. Compared with ALDH(low) TECs, ALDH(high) TECs formed more tubes on Matrigel-coated plates and sustained the tubular networks longer. Furthermore, VEGFR2 expression was higher in ALDHhigh TECs than that in ALDH(low) TECs. In addition, ALDH was expressed in the tumor blood vessels of in vivo mouse models of melanoma and oral carcinoma, but not in normal blood vessels. These findings indicate that ALDH(high) TECs exhibit an angiogenic phenotype. Stem-like TECs may have an essential role in tumor angiogenesis.
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 4.0 International
PISSN	1932-6203
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1371/journal.pone.0113910