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Infantile hemangioma-derived stem cells and endothelial cells are inhibited by class 3 semaphorins

机译:婴儿血管瘤衍生的干细胞和内皮细胞被3类血管素抑制

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摘要

Class 3 semaphorins were discovered as a family of axon guidance molecules, but are now known to be involved in diverse biologic processes. In this study, we investigated the anti-angiogenic potential of SEMA3E and SEMA3F (SEMA3E&F) in infantile hemangioma (IH). IH is a common vascular tumor that involves both vasculogenesis and angiogenesis. Our lab has identified and isolated hemangioma stem cells (HemSC), glucose transporter 1 positive (GLUT1(+)) endothelial cells (designated as GLUT1(sel) cells) based on anti-GLUT1 magnetic beads selection and GLUT1-negative endothelial cells (named HemEC). We have shown that these types of cells play important roles in hemangiogenesis. We report here that SEMA3E inhibited HemEC migration and proliferation while SEMA3F was able to suppress the migration and proliferation in all three types of cells. Confocal microscopy showed that stress fibers in HemEC were reduced by SEMA3E&F and that stress fibers in HemSC were decreased by SEMA3F, which led to cytoskeletal collapse and loss of cell motility in both cell types. Additionally, SEMA3E&F were able to inhibit vascular endothelial growth factor (VEGF)-induced sprouts in all three types of cells. Further, SEMA3E&F reduced the level of p-VEGFR2 and its downstream p-ERK in HemEC. These results demonstrate that SEMA3E&F inhibit IH cell proliferation and suppress the angiogenic activities of migration and sprout formation. SEMA3E&F may have therapeutic potential to treat or prevent growth of highly proliferative IH.
机译:3级半曲线素被发现为一个轴突引导分子系列,但现在已知参与不同的生物过程。在这项研究中,我们研究了Sema3e和Sema3f(Sema3e&F)的抗血管生成潜力在婴儿血管瘤(Ih)。 IH是一种常见的血管肿瘤,包括血管发生和血管生成。我们的实验室已鉴定并孤立的血管瘤干细胞(Hemsc),葡萄糖转运蛋白1阳性(Glut1(+))内皮细胞(指定为Glut1(SEL)细胞),基于抗Glut1磁珠选择和Glut1阴性内皮细胞(命名为hemec)。我们已经表明,这些类型的细胞在血管生成中起重要作用。我们在此报道,Sema3e抑制了Hemec迁移和增殖,同时Sema3F能够抑制所有三种类型的细胞中的迁移和增殖。共聚焦显微镜表明,通过SEMA3E&F降低了Hemec中的应力纤维,SEMO3F降低了HEMSC中的应力纤维,这导致了两种细胞类型中的细胞骨骼塌陷和细胞运动丧失。另外,SEMA3E&F能够在所有三种类型的细胞中抑制血管内皮生长因子(VEGF)诱导的芽。此外,SEMA3E&F在Hemec中降低了P-VEGFR2的水平及其下游P-ERK。这些结果表明SEMA3E&F抑制IH细胞增殖,抑制迁移和萌芽形成的血管生成活性。 SEMA3E&F可能具有治疗或预防高增殖物Ih的生长的治疗潜力。

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