Abstract

Rhabdomyosarcomas (RMS) are phenotypically and functionally heterogeneous. Both primary human RMS cultures and low-passage mouse RMS cell lines, which express the fusion oncoprotein Pax3:Foxo1 and lack the tumor suppressor (), exhibit marked heterogeneity in () expression at the single cell level. In mouse RMS cells, expression is directed by the promoter and coupled to YFP/P3F 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/P3F compared with YFP/P3F cells. Both YFP/P3F and YFP/P3F cells gave rise to mixed clones in vitro, consistent with fluctuations in expression over time. Exposure to the anti-tropomyosin compound TR100 disrupted the cytoskeleton and reversed enhanced migration and adhesion of YFP/P3F RMS cells. Heterogeneous expression of at the single cell level may provide a critical advantage during tumor progression.