Li Bo, Zhao Wei-Dong, Tan Zhi-Min, Fang Wen-Gang, Zhu Li, Chen Yu-Hua
Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, 92 Bei Er Road, Shenyang, Liaoning 110001, PR China.
FEBS Lett. 2006 Jul 24;580(17):4252-60. doi: 10.1016/j.febslet.2006.06.056. Epub 2006 Jun 30.
Small cell lung cancer (SCLC) cells migration across human brain microvascular endothelial cells (HBMECs) is an essential step of brain metastases. Here we investigated signalling pathways in HBMECs contributing to the process. Inhibition of endothelial Rho kinase (ROCK) with Y27632 and overexpression of ROCK dominant-negative mutant prevented SCLC cells, NCI-H209, transendothelial migration and the concomitant changes of tight junction. Conversely, inhibition of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) had no effects. Furthermore, endothelial RhoA protein was activated during NCI-H209 cells transendothelial migration. Rho/ROCK participated in NCI-H209 cells transendothelial migration through regulating actin cytoskeleton reorganization. These results suggested that Rho/ROCK was required for SCLC cells transendothelial migration.
小细胞肺癌（SCLC）细胞穿越人脑微血管内皮细胞（HBMECs）的迁移是脑转移的关键步骤。在此，我们研究了HBMECs中促成该过程的信号通路。用Y27632抑制内皮型Rho激酶（ROCK）以及过表达ROCK显性负性突变体可阻止SCLC细胞NCI-H209的跨内皮迁移以及紧密连接的相应变化。相反，抑制磷脂酰肌醇3-激酶（PI3K）和蛋白激酶C（PKC）则没有效果。此外，在NCI-H209细胞跨内皮迁移过程中，内皮型RhoA蛋白被激活。Rho/ROCK通过调节肌动蛋白细胞骨架重排参与NCI-H209细胞的跨内皮迁移。这些结果表明，Rho/ROCK是SCLC细胞跨内皮迁移所必需的。
