Zheng Li-Chun, Wang Xiao-Qing, Lu Kun, Deng Xiao-Ling, Zhang Cheng-Wei, Luo Hong, Xu Xu-Dong, Chen Xiao-Man, Yan Lu, Wang Yi-Qing, Shi Song-Lin
Medical College of Xiamen University, Jinshan Community Health Service Center, Xiamen Traditional Chinese Medical Hospital, Xiamen 361000, P.R. China.
Xiamen Heart Center, Medical College of Xiamen University, Xiamen 361000, P.R. China.
Oncotarget. 2017 Jun 20;8(25):41348-41363. doi: 10.18632/oncotarget.17298.
Tumor growth and metastasis are angiogenesis dependent. Angiogenic growth involves endothelial cell proliferation, migration, and invasion. Ephrin-B2 is a ligand for Eph receptor tyrosine kinases and is an important mediator in vascular endothelial growth factor-mediated angiogenesis. However, research offer controversial information regarding effects of ephrin-B2 on vascular endothelial cells. In this paper, proteome analyses showed that ephrin-B2/Fc significantly activates multiple signaling pathways related to cell proliferation, survival, and migration and suppresses apoptosis and cell death. Cytological experiments further confirm that ephrin-B2/Fc stimulates endothelial cell proliferation, triggers dose-dependent migration, and suppresses cell apoptosis. Results demonstrate that soluble dose-dependent ephrinB2 can promote proliferation and migration and inhibit apoptosis of human umbilical vein endothelial cells. These results also suggest that ephrinB2 prevents ischemic disease and can potentially be a new therapeutic target for treating angiogenesis-related diseases and tumors.
肿瘤生长和转移依赖于血管生成。血管生成性生长涉及内皮细胞的增殖、迁移和侵袭。Ephrin-B2是Eph受体酪氨酸激酶的配体,是血管内皮生长因子介导的血管生成中的重要介质。然而,关于ephrin-B2对血管内皮细胞的影响,研究提供了有争议的信息。在本文中,蛋白质组分析表明,ephrin-B2/Fc显著激活与细胞增殖、存活和迁移相关的多种信号通路,并抑制细胞凋亡和细胞死亡。细胞学实验进一步证实,ephrin-B2/Fc刺激内皮细胞增殖,引发剂量依赖性迁移,并抑制细胞凋亡。结果表明,可溶性剂量依赖性ephrinB2可促进人脐静脉内皮细胞的增殖和迁移,并抑制其凋亡。这些结果还表明,ephrinB2可预防缺血性疾病,并且有可能成为治疗血管生成相关疾病和肿瘤的新治疗靶点。