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首页> 外文期刊>Journal of Cellular Physiology >Osteosarcoma cells induce endothelial cell proliferation during neo-angiogenesis
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Osteosarcoma cells induce endothelial cell proliferation during neo-angiogenesis

机译:骨肉瘤细胞诱导内皮细胞在增殖neo-angiogenesis

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摘要

Understanding the mechanisms inducing endothelial cell (EC) proliferation following tumor microenvironment stimuli may be important for the development of antiangiogenic therapies. Here, we show that cyclin-dependent kinase 2 and 5 (Cdk2, Cdk5) are important mediators of neoangiogenesis in in vitro and in vivo systems. Furthermore, we demonstrate that a specific Yin Yang 1 (YY1) protein-dependent signal from osteosarcoma (SaOS) cells determines proliferation of human aortic endothelial cells (HAECs). Following tumor cell stimuli, HAECs overexpress Cdk2 and Cdk5, display increased Cdk2 activity, undergo enhanced proliferation, and form capillary-like structures. Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. Furthermore, Roscovitine decreased HAEC proliferation and angiogenesis (the latter by 70% in in vitro and 50% in in vivo systems; P<0.01 vs. control). Finally, the finding that Roscovitine triggers apoptosis in SaOS cells as well as in HAECs by activating caspase-3/7 indicates multiple mechanisms for the potential antitumoral effect of Roscovitine. Present work suggests that Cdk2 and Cdk5 might be pharmacologically accessible targets for both antiangiogenic and antitumor therapy.
机译:理解的机制诱导内皮肿瘤细胞(EC)扩散后微环境刺激可能是重要的抗血管新生疗法的发展。表明,细胞周期蛋白依赖性激酶2和5 (Cdk2、Cdk5)是neoangiogenesis的重要介质在体外和体内的系统。表明一个特定的阴阳1 (YY1)protein-dependent信号从骨肉瘤(巴西)细胞决定人类主动脉的扩散内皮细胞(HAECs)。刺激,HAECs过多表达Cdk2 Cdk5,显示Cdk2活动增加,进行增强扩散,形成capillary-like结构。Cdks,削弱了过度Cdk2 Cdk5和Cdk2活动YY1-dependent引发的信号由圣分泌细胞。Roscovitine HAEC核扩散和下降在体外血管生成(后者70%50%体内系统;最后,发现Roscovitine触发器圣细胞凋亡以及HAECs激活caspase-3/7显示多个潜在antitumoral效应的机制Roscovitine。和Cdk5药物可访问目标反血管增生和抗肿瘤治疗。

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