Pro-angiogenic signaling by the endothelial presence of CEACAM1
Pro-angiogenic signaling by the endothelial presence of CEACAM1
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DOI：
10.1074/jbc.m409407200
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发表时间：
2005-01-21
影响因子：
4.8
通讯作者：
Ergun, S
中科院分区：
文献类型：
--
作者：
Kilic, N;Oliveira-Ferrer, L;Ergun, S
在这里，我们展示了癌胚抗原相关细胞黏附分子-1(CEACAM1)在新生血管中的表达，但在肿瘤组织内的大血管中没有表达。相应地，只有参与体外管形成的人微血管内皮细胞才表现出CEACAM1。CEACAM1过表达的人微血管内皮细胞与CEACAM1沉默的人微血管内皮细胞用于迁移和管状形成分析。高表达CEACAM1的微血管内皮细胞在血管内皮生长因子(VEGF)刺激下存活时间延长，管腔形成增加，而通过小干扰RNA沉默CEACAM1可阻断这些作用。基因芯片和LightCycler分析表明，在CEACAM1高表达的微血管内皮细胞中，血管生成因子如VEGF、VEGF受体2、血管生成素-1、血管生成素-2、Tie-2、血管生成素和白介素8上调，而XVIII胶原/内皮抑素和Tie-1下调。Western印迹分析证实了这些结果在蛋白水平上的VEGF和内皮抑素。这些结果表明，CEACAM1在微血管内皮细胞中的结构性表达使其转变为血管生成表型，而CEACAM1的沉默明显取消了血管形成过程中血管内皮生长因子诱导的形态发生效应。因此，针对CEACAM1内皮细胞上调的策略在抗血管生成肿瘤治疗中可能是有前景的。
Here, we demonstrate the expression of carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) in angiogenic sprouts but not in large mother blood vessels within tumor tissue. Correspondingly, only human microvascular endothelial cells involved in in vitro tube formation exhibit CEACAM1. CEACAM1-overexpressing versus CEACAM1-silenced human microvascular endothelial cells were used in migration and tube formation assays. CEACAM1-overexpressing microvascular endothelial cells showed prolonged survival and increased tube formation when they were stimulated with vascular endothelial growth factor ( VEGF), whereas CEACAM1 silencing via small interfering RNA blocks these effects. Gene array and LightCycler analyses show an up-regulation of angiogenic factors such as VEGF, VEGF receptor 2, angiopoietin-1, angiopoietin-2, tie-2, angiogenin, and interleukin-8 but a down-regulation of collagen XVIII/endostatin and Tie-1 in CEACAM1-overexpressing microvascular endothelial cells. Western blot analyses confirm these results for VEGF and endostatin at the protein level. These results suggest that constitutive expression of CEACAM1 in microvascular endothelial cells switches them to an angiogenic phenotype, whereas CEACAM1 silencing apparently abrogates the VEGF-induced morphogenetic effects during capillary formation. Thus, strategies targeting the endothelial up-regulation of CEACAM1 might be promising for antiangiogenic tumor therapy.