| 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
|
| リソース情報 |
| ヒト・動物細胞 |
HSC-3(RCB1975) |
