Small GTPase R-Ras regulates integrity and functionality of tumor blood vessels.

Small GTPase R-Ras regulates integrity and functionality of tumor blood vessels.
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DOI:
10.1016/j.ccr.2012.06.013
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发表时间:
2012-08-14
期刊:
影响因子:
50.3
通讯作者:
Komatsu M
Komatsu M
中科院分区:
医学1区
文献类型:
--
作者:
Sawada J;Urakami T;Li F;Urakami A;Zhu W;Fukuda M;Li DY;Ruoslahti E;Komatsu M

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我们发现,R-RAS是RAS家族的一种小的GTP酶,对于肿瘤中成熟的、有功能的血管的建立是必不可少的。R-RAS基因的破坏严重损害了小鼠肿瘤血管的成熟过程。相反,R-RAS功能的增强通过增强内皮屏障功能和周细胞与新生血管的结合,改善了血管结构和血液灌注量,阻止了血浆渗漏。因此,R-RAS促进肿瘤血管的正常化。这些发现表明,在肿瘤血管形成过程中,R-RAS是血管完整性和功能的关键调节因子。
We show that R-Ras, a small GTPase of the Ras family, is essential for the establishment of mature, functional blood vessels in tumors. The genetic disruption of R-Ras severely impaired the maturation processes of tumor vessels in mice. Conversely, the gain of function of R-Ras improved vessel structure and blood perfusion and blocked plasma leakage by enhanced endothelial barrier function and pericyte association with nascent blood vessels. Thus, R-Ras promotes normalization of the tumor vasculature. These findings identify R-Ras as a critical regulator of vessel integrity and function during tumor vascularization.
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