Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells
Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells
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DOI：
10.1016/j.yexcr.2007.06.001
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发表时间：
2007-09-10
影响因子：
3.7
通讯作者：
Miura, Masahiko
中科院分区：
文献类型：
--
作者：
Igrashi, Kaori;Sakimoto, Ippei;Miura, Masahiko
电离辐射（IR）对肿瘤血管生成的影响仍然是未知的。在这项研究中，我们发现，IR（8戈伊）诱导血管内皮细胞（EC）进行指数生长的高频率（80-90%）衰老样表型。这一发现使我们能够通过检查这些EC的基因表达谱和体外血管生成活性来表征IR诱导的衰老样（IRSL）表型。与细胞周期进程和DNA复制相关的基因的表达水平在IRSL EC中显著降低。此外，这些细胞通过Matrigel的体外侵袭和迁移活性被显著抑制。我们还发现，汇合的EC表现出高频率IRSL表型时，他们在照射后立即重新铺板，而在平台期条件下孵育减少了这种表型的诱导和增强集落形成。DNA双链断裂修复的动力学，这表明一个更快的时间过程中融合的EC比在不断增长的EC，可能有助于保护机制与IRSL表型。这些结果表明，IRSL表型可能是重要的，以确定血管生成活性的内皮细胞照射后。本研究有助于进一步了解IR对肿瘤血管生成的影响。(c)2007年爱思唯尔公司All rights reserved.
The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high-frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. The expression levels of genes associated with cell cycle progression and DNA replication were remarkably reduced in the IRSL ECs. Additionally, the in vitro invasion and migration activities of these cells through Matrigel were significantly suppressed. We also found that confluent ECs exhibited a high-frequency IRSL phenotype when they were replated immediately after irradiation, whereas incubation in plateau-phase conditions reduced the induction of this phenotype and enhanced colony formation. The kinetics of DNA double-strand break repair, which showed a faster time course in confluent ECs than in growing ECs, may contribute to the protective mechanism associated with the IRSL phenotype. These results imply that the IRSL phenotype may be important for determining the angiogenic activity of ECs following irradiation. The present study should contribute to the understanding of the effects of IR on tumor angiogenesis. (c) 2007 Elsevier Inc. All rights reserved.