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

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Title: Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype
Authors: Ohmura-Kakutani, Hitomi Browse this author
Akiyama, Kosuke Browse this author →KAKEN DB
Maishi, Nako Browse this author →KAKEN DB
Ohga, Noritaka Browse this author →KAKEN DB
Hida, Yasuhiro Browse this author →KAKEN DB
Kawamoto, Taisuke Browse this author
Iida, Junichiro Browse this author →KAKEN DB
Shindoh, Masanobu Browse this author →KAKEN DB
Tsuchiya, Kunihiko Browse this author
Shinohara, Nobuo Browse this author →KAKEN DB
Hida, Kyoko Browse this author →KAKEN DB
Issue Date: 1-Dec-2014
Publisher: Public Library of Science
Journal Title: PLOS one
Volume: 9
Issue: 12
Start Page: e113910
Publisher DOI: 10.1371/journal.pone.0113910
Abstract: 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.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/57970
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 樋田 京子

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