期刊
ANGIOGENESIS
卷 17, 期 2, 页码 407-418出版社
SPRINGER
DOI: 10.1007/s10456-013-9386-1
关键词
Lymphatic endothelial cells (LECs); Interleukin-6 (IL-6); Vascular endothelial growth factor-C (VEGF-C); Lymphangiogenesis; Src
资金
- National Science Council of Taiwan [NSC98-2320-B-038-007]
- Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan [100TMU-WFH-01-4]
- Landseed Hospital, Taoyuan, Taiwan [LSH-2012-04]
Formation of lymphatic capillaries by lymphatic endothelial cells (LECs) occurs both in normal tissues as well as in pathological processes including tumor metastasis. Interleukin-6 (IL-6), a potent pro-inflammatory cytokine, has been shown to be highly elevated in various cancers. IL-6 has also been shown to increase tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. Although lymphangiogenesis is associated with lymph node metastasis and also resistance to conventional therapy in various cancers, the precise mechanisms of lymphangiogenesis in LECs remain unclear. This study aimed to investigate the signaling cascade involved in IL-6-induced VEGF-C expression in murine LECs (SV-LEC). The VEGF-C mRNA and protein levels were increased in SV-LECs exposed to IL-6. IL-6 time-dependently induced Src phosphorylation and downstream phosphorylation of ERK1/2 and p38MAPK. In contrast, PP2, an inhibitor of Src signaling, abrogated IL-6's effects on ERK1/2 and p38MAPK phosphorylation. IL-6 exposure also led to increase in VEGF-C promoter-luciferase activity as well as C/EBP beta- and kappa B-luciferase activities. VEGF-C promoter-, C/EBP beta- and kappa B-luciferase activities were all suppressed by Src, ERK1/2 or p38MAPK signaling blockades despite presence of IL-6. Finally, C/EBP beta and p65 binding to the VEGF-C promoter region were increased after IL-6 exposure in SV-LECs. Taken together, we report a Src-mediated ERK1/2 and p38MAPK activation resulting in C/EBP beta and p65 binding to the promoter region of VEGF-C, leading to VEGF-C expression in IL-6-exposed SV-LECs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据