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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)
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Submitter: 樋田 京子
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