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Publication

Muscle Stem Cells Give Rise to Rhabdomyosarcomas in a Severe Mouse Model of Duchenne Muscular Dystrophy.

Francesca Boscolo Sesillo | David Fox | Alessandra Sacco

Cell reports | 2019

Most human cancers originate from high-turnover tissues, while low-proliferating tissues, like skeletal muscle, exhibit a lower incidence of tumor development. In Duchenne muscular dystrophy (DMD), which induces increased skeletal muscle regeneration, tumor incidence is increased. Rhabdomyosarcomas (RMSs), a rare and aggressive type of soft tissue sarcoma, can develop in this context, but the impact of DMD severity on RMS development and its cell of origin are poorly understood. Here, we show that RMS latency is affected by DMD severity and that muscle stem cells (MuSCs) can give rise to RMS in dystrophic mice. We report that even before tumor formation, MuSCs exhibit increased self-renewal and an expression signature associated with RMSs. These cells can form tumorspheres in vitro and give rise to RMSs in vivo. Finally, we show that the inflammatory genes Ccl11 and Rgs5 are involved in RMS growth. Together, our results show that DMD severity drives MuSC-mediated RMS development.

Pubmed ID: 30650360 RIS Download

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Associated grants

Agency: NIAMS NIH HHS, United States
Id: P30 AR061303
Agency: NCI NIH HHS, United States
Id: P30 CA030199
Agency: NIAMS NIH HHS, United States
Id: R01 AR064873

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