論文

査読有り
2014年12月

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

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

9
12
開始ページ
e113910
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0113910
出版者・発行元
PUBLIC LIBRARY SCIENCE

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.

Web of Science ® 被引用回数 : 22

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0113910
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25437864
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000347114900094&DestApp=WOS_CPL

エクスポート
BibTeX RIS