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首页> 外文期刊>Brain research >TSP2 acts as a suppresser of cell invasion, migration and angiogenesis in medulloblastoma by inhibiting the Notch signaling pathway
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TSP2 acts as a suppresser of cell invasion, migration and angiogenesis in medulloblastoma by inhibiting the Notch signaling pathway

机译：TSP2通过抑制凹口信号通路，作为Medulloblastoma的细胞侵袭，迁移和血管生成的抑制剂

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摘要

Medulloblastoma (MB) represents a fatal malignancy often occurring in children. Angiogenesis is a hallmark of the progression of MB. Over the past decade, investigators have attempted to develop more effective and less toxic anti-angiogenic strategies to treat MB. Thrombospondin (TSP) family is observed to be a key regulator of angiogenesis. Thus, the current study aimed to elucidate the function of TSP2 in patients with MB and the underlying mechanism. The expression of TSP2, Notch1 and VEGF in MB and adjacent tissues collected from clinical samples as well as a MB cell line (Daoy) was examined. The results demonstrated that in the MB tissues and Daoy cells, TSP2 was downregulated, while Notchi and VEGF were upregulated. Then, after the Daoy cells were treated with TSP2 silencing, TSP2 overexpression, or Notch signaling pathway inhibition, a series of in vitro cell experiments were performed to verify the interaction between TSP2 and Notch signaling pathway, and to examine the abilities of cell proliferation, migration, invasion, and tube formation. Upregulation of TSP2 was observed to lead to the downregulation of the Notch signaling pathway. Moreover, cells overexpressing TSP2 exhibited diminished proliferation, invasion, migration, and tube formation. In addition, a significant attenuation of tumor growth and angiogenesis was identified in vivo in the Daoy cells overexpressing TSP2 inoculated in nude mice. Taken together, the key findings of this study revealed the inhibitory role of TSP2 in the development of MB via blockade of the Notch signaling pathway, highlighting its potential as a treatment target for MB treatment.
机译：Medulloblastoma（MB）代表致命恶性肿瘤常常发生在儿童中。血管生成是MB进展的标志。在过去十年中，调查人员试图开发更有效和更少有毒的抗血管生成策略来治疗MB。观察到血栓化素（TSP）系列是血管生成的关键调节剂。因此，目前的研究旨在阐明MB和潜在机制患者TSP2的功能。检查了从临床样品中收集的MB和相邻组织中TSP2，Notch1和VEGF的表达以及MB细胞系（Daoy）。结果证明，在MB组织和甲醛细胞中，TSP2被下调，同时上调Notchi和VEGF。然后，在用TSP2沉默的Daoy细胞处理后，TSP2过表达或Notch信号传导途径抑制后，进行一系列体外细胞实验以验证TSP2和Notch信号通路之间的相互作用，并检查细胞增殖的能力，迁移，入侵和管形成。观察到TSP2的上调，以导致陷波信号通路的下调。此外，过表达TSP2的细胞表现出增生，侵袭，迁移和管形成。此外，在过表达在裸鼠中接种的DSOOY细胞的Daoy细胞中鉴定了肿瘤生长和血管生成的显着衰减。本研究的关键发现揭示了TSP2在MB的开发中的抑制作用，通过阻断陷波信号通路，突出了其作为MB治疗的治疗靶标的潜力。

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  • 来源
    《Brain research》 |2019年第2019期|共8页
  • 作者

    Pan Wei; Song Xing-Yu; Hu Qi-Bo; Zhang Meng; Xu Xiao-Heng;

  • 作者单位

    Jilin Univ Hosp 2 Dept Pediat 218 Ziqiang St Changchun 130041 Jilin Peoples R China;

    Jilin Univ Hosp 2 Dept Pediat 218 Ziqiang St Changchun 130041 Jilin Peoples R China;

    Jilin Univ Hosp 2 Dept Pediat 218 Ziqiang St Changchun 130041 Jilin Peoples R China;

    Jilin Univ Hosp 2 Dept Pediat 218 Ziqiang St Changchun 130041 Jilin Peoples R China;

    Jilin Univ Hosp 2 Dept Pediat 218 Ziqiang St Changchun 130041 Jilin Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

    TSP2; Notch signaling pathway; Medulloblastoma; Invasion; Migration; Angiogenesis;

    机译：TSP2;缺口信号通路;髓质母细胞瘤;侵袭;迁移;血管生成;

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