细胞外囊泡相关的IGF2BP3调节了Ewing肉瘤细胞迁移,并影响邻近细胞中的PI3K/Akt通路
Caterina Mancarella1, Veronica Giusti1, Giulia Caldoni1
1Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Cancer gene therapy
|June 23, 2023
概括
细胞外囊中的胰岛素样生长因子2mRNA结合蛋白3 (IGF2BP3) 影响了尤文肉瘤细胞的迁移和通信,可能导致瘤异质.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 尤文肉瘤 (EWS) 呈现出显著的瘤内部异质性,使治疗复杂化.
- RNA结合蛋白IGF2BP3的高表达与EWS的不良预后和转移有关.
- 导致EWS异质性的细胞间通信机制尚未完全理解.
研究的目的:
- 调查IGF2BP3作为易溶性介质在尤宁肉瘤内的细胞间通信中的作用.
- 确定IGF2BP3及其相关的细胞外囊泡 (EVs) 对EWS细胞行为和分子通路的影响.
主要方法:
- 来自EWS细胞的细胞超级和细胞外囊泡 (EVs) 中IGF2BP3的量化.
- 从IGF2BP3阳性和阴性EWS细胞中EVs对受体EWS细胞迁移和增殖的影响的评估.
- 在来自IGF2BP3沉默细胞的EV中分析miRNA载荷.
- 研究这些EV对受体细胞PI3K/Akt信号通路的影响.
- 在EWS中差异表达的miRNA与临床EWS组织样本的相关性分析.
主要成果:
- IGF2BP3由EWS细胞分泌,并被包装在EVs中.
- 来自EWS细胞的EVs调节受体细胞迁移,但不增殖,以一种取决于IGF2BP3表达的方式.
- 来自IGF2BP3沉默细胞的EVs表现出改变的miRNA配置文件,并抑制PI3K/Akt通路.
- 在EWS中的特定miRNA签名与IGF2BP3表达水平相关,并且可以区分EWS临床亚型.
结论:
- 通过EVs释放的IGF2BP3在Ewing肉瘤中介细胞间通信起作用.
- 通过EV介导的IGF2BP3及其相关miRNA的转移有助于在EWS中观察到的表型异质性.
- 这些发现突出了IGF2BP3和EVs作为理解和潜在地治疗EWS异质性的潜在目标.
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