論文 - 詳細
| RRC ID | 62226 |
|---|---|
| 著者 | Kondoh M, Ohga N, Akiyama K, Hida Y, Maishi N, Towfik AM, Inoue N, Shindoh M, Hida K. |
| タイトル | Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment. |
| ジャーナル | PLoS One |
| 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. |
| 巻・号 | 8(11) |
| ページ | e80349 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0080349 |
| PII | PONE-D-13-29910 |
| PMID | 24260373 |
| PMC | PMC3829944 |
| MeSH | Animals Cell Cycle / genetics Chromosome Aberrations* Chromosomes, Human, Pair 17 / genetics* Endothelial Cells / metabolism* Humans Hypoxia / metabolism Hypoxia / physiopathology* Hypoxia-Inducible Factor 1 / metabolism Karyotype Mice Reactive Oxygen Species / metabolism* Tumor Cells, Cultured Tumor Microenvironment / genetics* Vascular Endothelial Growth Factor A / metabolism Vascular Endothelial Growth Factor Receptor-2 / metabolism |
| IF | 2.74 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HSC-3(RCB1975) |