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

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Title: Hypoxia-Induced Reactive Oxygen Species Cause Chromosomal Abnormalities in Endothelial Cells in the Tumor Microenvironment
Authors: Kondoh, Miyako Browse this author
Ohga, Noritaka Browse this author →KAKEN DB
Akiyama, Kosuke Browse this author
Hida, Yasuhiro Browse this author →KAKEN DB
Maishi, Nako Browse this author →KAKEN DB
Towfik, Alam Mohammad Browse this author
Inoue, Nobuo Browse this author →KAKEN DB
Shindoh, Masanobu Browse this author →KAKEN DB
Hida, Kyoko Browse this author →KAKEN DB
Issue Date: 15-Nov-2013
Publisher: Public library science
Journal Title: Plos one
Volume: 8
Issue: 11
Start Page: e80349
Publisher DOI: 10.1371/journal.pone.0080349
PMID: 24260373
Abstract: 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.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/54546
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 樋田 京子

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