Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment.
Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment.
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DOI：
10.1371/journal.pone.0080349
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hida K
中科院分区：
文献类型：
--
作者：
Kondoh M;Ohga N;Akiyama K;Hida Y;Maishi N;Towfik AM;Inoue N;Shindoh M;Hida K
有许多证据表明，肿瘤微环境中的缺氧促进肿瘤进展。在早期的研究中，我们报道了肿瘤相关内皮细胞的异常表型，如对化疗耐药和染色体不稳定。在这里，我们调查的作用，缺氧的收购染色体异常的内皮细胞。从人肿瘤异种移植物中分离的肿瘤相关内皮细胞显示染色体异常，其中>30%为非整倍体。肿瘤相关内皮细胞的非整倍体也显示了同步原位杂交17号染色体和免疫组化抗CD 31抗体内皮染色。非整倍体细胞被哌莫尼达唑阳性区域包围，表明缺氧。人微血管内皮细胞表达缺氧诱导因子1和血管内皮生长因子A在缺氧或缺氧-复氧反应，并在这些条件下，他们获得非整倍体在7天。通过血管内皮生长因子受体2抑制剂抑制血管内皮生长因子信号传导或通过N-乙酰-L-半胱氨酸抑制活性氧来抑制非整倍体的诱导。这些结果表明，缺氧通过诱导活性氧和肿瘤微环境中血管内皮生长因子的过度信号传导诱导内皮细胞染色体异常。
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.
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影响因子：
3.7
作者：
Kawamoto T;Ohga N;Akiyama K;Hirata N;Kitahara S;Maishi N;Osawa T;Yamamoto K;Kondoh M;Shindoh M;Hida Y;Hida K
通讯作者：
Hida K
影响因子：
4.8
作者：
El-Remessy, A. B.;Al-Shabrawey, M.;Caldwell, R. B.
通讯作者：
Caldwell, R. B.
影响因子：
2.6
作者：
BROWN, JM
通讯作者：
BROWN, JM
影响因子：
50.3
作者：
Blouw, B;Song, HQ;Bergers, G
通讯作者：
Bergers, G
影响因子：
4.7
作者：
Bussolati, Benedetta;Assenzio, Barbara;Carnussi, Giovanni
通讯作者：
Carnussi, Giovanni