Magic roundabout, a tumor endothelial marker: Expression and signaling
Magic roundabout, a tumor endothelial marker: Expression and signaling
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DOI：
10.1016/j.bbrc.2005.03.250
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发表时间：
2005-07-01
影响因子：
3.1
通讯作者：
Sukhatme, VP
中科院分区：
文献类型：
--
作者：
Seth, P;Lin, YF;Sukhatme, VP
引导血管到达特定路径的分子信号尚未完全破译，但被认为与介导神经元引导的信号相似。这些信号不仅对正常的血管发育至关重要，而且在肿瘤血管生成中也起重要作用。在这项研究中，我们已经证明了Robo家族成员Magic Roundabout（MRB）的肿瘤内皮特异性表达，功能上表征了其在内皮细胞迁移中的作用，并定义了可能介导该功能的信号通路。我们发现，在许多实体瘤中，MRB在肿瘤内皮细胞与正常成人内皮细胞中差异过表达。此外，MRB在内皮细胞中的过表达以配体非依赖性方式激活MRB，并且MRB通过Slit 2（一种推定配体）的激活导致VEGF和FGF诱导的迁移的抑制。我们还证明，MRB诱导的内皮细胞迁移的抑制部分介导的Ras-Raf-Mek-Erk信号通路。因此，我们推测MRB的表达参与调节肿瘤血管生成过程中内皮细胞的迁移。(C)2005年爱思唯尔公司All rights reserved.
Molecular signals that guide blood vessels to specific paths are not fully deciphered, but are thought to be similar to signals that mediate neuronal guidance. These cues are not only critical for normal blood vessel development, but rnay also play a major role ill tumor angiogenesis. In this Study, we have demonstrated the tumor endothelial specific expression of a Robo family member, magic roundabout (MRB), functionally characterized its role in endothelial cell migration and defined a signaling pathway that might mediate this function. We show that MRB is differentially over-expressed in tumor endothelial cells versus normal adult endothelial cells in numerous solid tumors. Moreover, over-expression of MRB in endothelial cells activates MRB in a ligand-independent fashion, and activation of MRB via Slit2, a Putative ligand, results in inhibition of VEGF and FGF induced migration. We also demonstrate that MRB induced inhibition of endothelial migration is partially mediated by the Ras-Raf-Mek-Erk signaling pathway. We therefore hypothesize that expression of MRB is involved in regulating the migration of endothelial cells during tumor angiogenesis. (C) 2005 Elsevier Inc. All rights reserved.