源自肌肉干细胞和祖细胞的不同且重叠的肉瘤亚型。
Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells.
机构信息
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA; Program in Molecular Cancer Biology, Duke University, Durham, NC 27710, USA.
出版信息
Cell Rep. 2013 Nov 27;5(4):933-40. doi: 10.1016/j.celrep.2013.10.020. Epub 2013 Nov 14.
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, whereas undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue sarcomas diagnosed in adults. To investigate the myogenic cell(s) of origin of these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7(+) and MyoD(+) myogenic progenitors by expressing oncogenic Kras(G12D) and deleting Trp53 in vivo. Pax7-CreER mice developed RMS and UPS, whereas MyoD-CreER mice developed UPS. Using gene set enrichment analysis, RMS and UPS each clustered specifically within their human counterparts. These results suggest that RMS and UPS have distinct and overlapping cells of origin within the muscle lineage. Taking them together, we have established mouse models of soft tissue sarcoma from muscle stem and progenitor cells.
摘要
横纹肌肉瘤 (RMS) 是儿童中最常见的软组织肉瘤，而未分化多形性肉瘤 (UPS) 是成人中最常见的软组织肉瘤之一。为了研究这些肉瘤的成肌细胞起源，我们使用 Pax7-CreER 和 MyoD-CreER 小鼠通过体内表达致癌性 Kras(G12D)和缺失 Trp53 来转化 Pax7(+)和 MyoD(+)成肌祖细胞。Pax7-CreER 小鼠发展为 RMS 和 UPS，而 MyoD-CreER 小鼠发展为 UPS。使用基因集富集分析，RMS 和 UPS 分别在其人类对应物中特异性聚类。这些结果表明，RMS 和 UPS 在肌肉谱系中有不同但重叠的细胞起源。综上所述，我们已经建立了源自肌肉干细胞和祖细胞的软组织肉瘤的小鼠模型。
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