Rhabdomyosarcomas (RMS) are phenotypically and functionally heterogeneous. Both primary human RMS cultures and low-passage Myf6Cre,Pax3:Foxo1,p53 mouse RMS cell lines, which express the fusion oncoprotein Pax3:Foxo1 and lack the tumor suppressor Tp53 (Myf6Cre,Pax3:Foxo1,p53), exhibit marked heterogeneity in PAX3:FOXO1 (P3F) expression at the single cell level. In mouse RMS cells, P3F expression is directed by the Pax3 promoter and coupled to eYFP YFP^low/P3F^low mouse RMS cells included 87% G0/G1 cells and reorganized their actin cytoskeleton to produce a cellular phenotype characterized by more efficient adhesion and migration. This translated into higher tumor-propagating cell frequencies of YFP^low/P3F^low compared with YFP^high/P3F^high cells. Both YFP^low/P3F^low and YFP^high/P3F^high cells gave rise to mixed clones in vitro, consistent with fluctuations in P3F expression over time. Exposure to the anti-tropomyosin compound TR100 disrupted the cytoskeleton and reversed enhanced migration and adhesion of YFP^low/P3F^low RMS cells. Heterogeneous expression of PAX3:FOXO1 at the single cell level may provide a critical advantage during tumor progression.

中文翻译：

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单细胞 PAX3:FOXO1 表达与横纹肌肉瘤致瘤性呈负相关。

横纹肌肉瘤 (RMS) 在表型和功能上具有异质性。原代人类 RMS 培养物和低传代Myf6Cre,Pax3:Foxo1,p53小鼠 RMS 细胞系均表达融合癌蛋白 Pax3:Foxo1 且缺乏肿瘤抑制因子Tp53 ( Myf6Cre,Pax3:Foxo1,p53 )，在PAX3 中表现出显着的异质性:FOXO1 ( P3F ) 在单细胞水平上的表达。在小鼠 RMS 细胞中，P3F表达由Pax3启动子引导并与eYFP YFP^低/P3F^低偶联小鼠 RMS 细胞包括 87% 的 G0/G1 细胞，并重组了它们的肌动蛋白细胞骨架以产生以更有效的粘附和迁移为特征的细胞表型。与 YFP^高/P3F^高细胞相比，这转化为 YFP^低/P3F^低的更高肿瘤传播细胞频率。YFP^低/P3F^低和 YFP^高/P3F^高细胞在体外产生混合克隆，这与P3F表达随时间的波动一致。暴露于抗原肌球蛋白化合物 TR100 会破坏细胞骨架并逆转 YFP^低/P3F^低的增强迁移和粘附RMS 细胞。PAX3:FOXO1在单细胞水平的异质表达可能在肿瘤进展过程中提供关键优势。