与癌症相关的纤维细胞状瘤细胞重塑了尤文肉瘤瘤微环境
Emma D Wrenn1, April A Apfelbaum1,2, Erin R Rudzinski3
1Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington.
概括
尤文肉瘤 (EwS) 细胞表现出转录异质性,CD73+亚群采用与癌症相关的纤维细胞类似的特性. 这种可塑性驱动瘤异质性,并在体内重新塑造瘤微环境.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 尤文肉瘤 (EwS) 具有有限的遗传和组织学异质性.
- 然而,EwS瘤细胞在体外显示出显著的转录异质性.
- 这种异质性涉及不同程度的介质细胞系特征.
研究的目的:
- 研究EWS细胞的转录异质性如何在体内促进瘤表型异质性.
- 为了识别与EWS细胞亚群相关的生物标志物.
- 了解EWS细胞可塑性在瘤微环境中的功能影响.
主要方法:
- 单细胞EWS细胞系的蛋白质基因组测序.
- 与患者瘤转录组数据的整合.
- 光激活细胞分类 (FACS) 用于分群隔离.
- 异种移植的数字空间分析和整个转录组分析.
- 异种移植和患者瘤的多重免疫光染色.
主要成果:
- CD73被确定为中酶体EWS细胞亚群的生物标志物.
- CD73+EWS细胞表现出不同的转录特征,包括EWS::FLI1抑制基因上调.
- CD73+细胞显示出增加的迁移潜力和母体基因表达.
- 这些细胞储存了丰富的细胞外基质 (ECM),类似于与癌症相关的纤维细胞 (CAF类细胞).
- 在患者的瘤中观察到CD73+细胞和ECM的异质分布,特别是在死核和侵入性区域附近.
结论:
- EwS瘤细胞可以获得与癌症相关的纤维细胞样 (CAF样) 特性.
- 独特的EwS细胞亚群有助于整体瘤异质性.
- 这种细胞可塑性在重塑瘤微环境方面发挥着作用.
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