Department of Molecular and Translational Medicine and Interuniversity Institute of Myology (IIM), University of Brescia, Viale Europa 11, Brescia, 25123, Italy.
Trends Mol Med. 2013 Sep;19(9):546-54. doi: 10.1016/j.molmed.2013.07.001. Epub 2013 Jul 23.
Several lines of recent evidence have opened a new debate on the mechanisms underlying the genesis of rhabdomyosarcoma, a pediatric soft tissue tumor with a widespread expression of muscle-specific markers. In particular, it is increasingly evident that the loss of skeletal muscle integrity observed in some mouse models of muscular dystrophy can favor rhabdomyosarcoma formation. This is especially true in old age. Here, we review these experimental findings and focus on the main molecular and cellular events that can dictate the tumorigenic process in dystrophic muscle, such as the loss of structural or regulatory proteins with tumor suppressor activity, the impaired DNA damage response due to oxidative stress, the chronic inflammation and the conflicting signals arising within the degenerated muscle niche.
最近的一些研究证据引发了一场新的争论，即探讨横纹肌肉瘤（一种具有广泛肌肉特异性标志物表达的小儿软组织肿瘤）发生的机制。特别是，越来越明显的是，在一些肌肉营养不良的小鼠模型中观察到的骨骼肌完整性丧失可能有利于横纹肌肉瘤的形成。在老年时尤其如此。在这里，我们回顾了这些实验结果，并重点介绍了可以决定肌肉营养不良中肿瘤发生过程的主要分子和细胞事件，例如具有肿瘤抑制活性的结构或调节蛋白的丧失、由于氧化应激导致的 DNA 损伤反应受损、慢性炎症以及退化肌肉龛位内产生的冲突信号。
