論文

査読有り 国際誌
2017年11月

Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance.

Cancer science
  • Kyoko Hida
  • ,
  • Nako Maishi
  • ,
  • Kosuke Akiyama
  • ,
  • Hitomi Ohmura-Kakutani
  • ,
  • Chisaho Torii
  • ,
  • Noritaka Ohga
  • ,
  • Takahiro Osawa
  • ,
  • Hiroshi Kikuchi
  • ,
  • Hirofumi Morimoto
  • ,
  • Masahiro Morimoto
  • ,
  • Masanobu Shindoh
  • ,
  • Nobuo Shinohara
  • ,
  • Yasuhiro Hida

108
11
開始ページ
2195
終了ページ
2203
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/cas.13388

Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TEC) exhibit several altered phenotypes compared with normal endothelial cells (NEC). For example, TEC have chromosomal abnormalities and are resistant to several anticancer drugs. Furthermore, TEC contain stem cell-like populations with high aldehyde dehydrogenase (ALDH) activity (ALDHhigh TEC). ALDHhigh TEC have proangiogenic properties compared with ALDHlow TEC. However, the association between ALDHhigh TEC and drug resistance remains unclear. In the present study, we found that ALDH mRNA expression and activity were higher in both human and mouse TEC than in NEC. Human NEC:human microvascular endothelial cells (HMVEC) were treated with tumor-conditioned medium (tumor CM). The ALDHhigh population increased along with upregulation of stem-related genes such as multidrug resistance 1, CD90, ALP, and Oct-4. Tumor CM also induced sphere-forming ability in HMVEC. Platelet-derived growth factor (PDGF)-A in tumor CM was shown to induce ALDH expression in HMVEC. Finally, ALDHhigh TEC were resistant to fluorouracil (5-FU) in vitro and in vivo. ALDHhigh TEC showed a higher grade of aneuploidy compared with that in ALDHlow TEC. These results suggested that tumor-secreting factor increases ALDHhigh TEC populations that are resistant to 5-FU. Therefore, ALDHhigh TEC in tumor blood vessels might be an important target to overcome or prevent drug resistance.

リンク情報
DOI
https://doi.org/10.1111/cas.13388
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28851003
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666026

エクスポート
BibTeX RIS