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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)
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Submitter: 樋田 京子
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