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Hypoxia-Induced Reactive Oxygen Species Cause Chromosomal Abnormalities in Endothelial Cells in the Tumor Microenvironment


pone.0080349.pdf3.17 MBPDF見る/開く

タイトル: Hypoxia-Induced Reactive Oxygen Species Cause Chromosomal Abnormalities in Endothelial Cells in the Tumor Microenvironment
著者: Kondoh, Miyako 著作を一覧する
Ohga, Noritaka 著作を一覧する
Akiyama, Kosuke 著作を一覧する
Hida, Yasuhiro 著作を一覧する
Maishi, Nako 著作を一覧する
Towfik, Alam Mohammad 著作を一覧する
Inoue, Nobuo 著作を一覧する
Shindoh, Masanobu 著作を一覧する
Hida, Kyoko 著作を一覧する
発行日: 2013年11月15日
出版者: Public library science
誌名: Plos one
巻: 8
号: 11
開始ページ: e80349
出版社 DOI: 10.1371/journal.pone.0080349
抄録: There is much evidence that hypoxia in the tumor microenvironment enhances tumor progression. In an earlier study, we reported abnormal phenotypes of tumor-associated endothelial cells such as those resistant to chemotherapy and chromosomal instability. Here we investigated the role of hypoxia in the acquisition of chromosomal abnormalities in endothelial cells. Tumor-associated endothelial cells isolated from human tumor xenografts showed chromosomal abnormalities, > 30% of which were aneuploidy. Aneuploidy of the tumor-associated endothelial cells was also shown by simultaneous in-situ hybridization for chromosome 17 and by immunohistochemistry with anti-CD31 antibody for endothelial staining. The aneuploid cells were surrounded by a pimonidazole-positive area, indicating hypoxia. Human microvascular endothelial cells expressed hypoxia-inducible factor 1 and vascular endothelial growth factor A in response to either hypoxia or hypoxia-reoxygenation, and in these conditions, they acquired aneuploidy in 7 days. Induction of aneuploidy was inhibited by either inhibition of vascular endothelial growth factor signaling with vascular endothelial growth factor receptor 2 inhibitor or by inhibition of reactive oxygen species by N-acetyl-L-cysteine. These results indicate that hypoxia induces chromosomal abnormalities in endothelial cells through the induction of reactive oxygen species and excess signaling of vascular endothelial growth factor in the tumor microenvironment.
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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