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J Clin Invest.:ID蛋白使胶质细胞瘤保持干细胞活性

  1. 微环境
  2. 胶质细胞瘤
  3. 锚定

来源:生物谷 2012-12-23 17:30

2012年12月23日讯 /生物谷BIOON/ --神经胶质细胞瘤是最常见的一类神经系统肿瘤。其发病迅猛,但是目前还没有有效治愈手段。肿瘤是由类似于神经干细胞的胶质细胞瘤形成细胞(glioma initiating cells ,GICs)组成。GIC只有在特殊的微环境下才能保持其干细胞活性,恶化癌症进程。

2012年12月23日讯 /生物谷BIOON/ --神经胶质细胞瘤是最常见的一类神经系统肿瘤。其发病迅猛,但是目前还没有有效治愈手段。肿瘤是由类似于神经干细胞的胶质细胞瘤形成细胞(glioma initiating cells ,GICs)组成。GIC只有在特殊的微环境下才能保持其干细胞活性,恶化癌症进程。

哥伦比亚大学Antonio Lavarone领导的研究组在Journal of Clinical Investigation发表文章,揭示了胶质瘤中的一类命名为ID蛋白的蛋白质在胶质瘤锚定中的作用。

用小鼠作为模型,研究人员发现ID蛋白负责将GIC锚定在特殊的微环境中,保持GIC的干细胞活性。在胶质细胞瘤病人中同样发现了调节ID蛋白基因的表达。

这些结果显示了ID蛋白在调控胶质细胞瘤发病进程中有重要作用,可能适于作为治疗靶点。(生物谷Bioon.com)

Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis

Niola F, Zhao X, Singh D, Sullivan R, Castano A, Verrico A, Zoppoli P, Friedmann-Morvinski D, Sulman E, Barrett L, Zhuang Y, Verma I, Benezra R, Aldape K, Iavarone A, Lasorella A.

High-grade gliomas (HGGs) are incurable brain tumors that are characterized by the presence of glioma-initiating cells (GICs). GICs are essential to tumor aggressiveness and retain the capacity for self-renewal and multilineage differentiation as long as they reside in the perivascular niche. ID proteins are master regulators of stemness and anchorage to the extracellular niche microenvironment, suggesting that they may play a role in maintaining GICs. Here, we modeled the probable therapeutic impact of ID inactivation in HGG by selective ablation of Id in tumor cells and after tumor initiation in a new mouse model of human mesenchymal HGG. Deletion of 3 Id genes induced rapid release of GICs from the perivascular niche, followed by tumor regression. GIC displacement was mediated by derepression of Rap1gap and subsequent inhibition of RAP1, a master regulator of cell adhesion. We identified a signature module of 5 genes in the ID pathway, including RAP1GAP, which segregated 2 subgroups of glioma patients with markedly different clinical outcomes. The model-informed survival analysis together with genetic and functional studies establish that ID activity is required for the maintenance of mesenchymal HGG and suggest that pharmacological inactivation of ID proteins could serve as a therapeutic strategy.

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