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

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タイトル: Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype
著者: Ohmura-Kakutani, Hitomi 著作を一覧する
Akiyama, Kosuke 著作を一覧する
Maishi, Nako 著作を一覧する
Ohga, Noritaka 著作を一覧する
Hida, Yasuhiro 著作を一覧する
Kawamoto, Taisuke 著作を一覧する
Iida, Junichiro 著作を一覧する
Shindoh, Masanobu 著作を一覧する
Tsuchiya, Kunihiko 著作を一覧する
Shinohara, Nobuo 著作を一覧する
Hida, Kyoko 著作を一覧する
発行日: 2014年12月 1日
出版者: Public Library of Science
誌名: PLOS one
巻: 9
号: 12
開始ページ: e113910
出版社 DOI: 10.1371/journal.pone.0113910
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.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 樋田 京子


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