Lim Chin Yan, Solter Davor, Knowles Barbara B, Damjanov Ivan
1 Epithelial Epigenetics and Development Lab, Institute of Medical Biology , A*STAR, Singapore , Singapore.
2 Department of Pathology, The University of Kansas School of Medicine , Kansas City, Kansas.
Stem Cells Dev. 2015 Jul 1;24(13):1515-20. doi: 10.1089/scd.2015.0033. Epub 2015 May 21.
The embryonic portion of 7-day-old mouse embryos transplanted to extrauterine sites of syngeneic adult animals gives rise to teratoid tumors, which may be either benign [teratomas (T)] or malignant [teratocarcinomas (TC)]. The incidence of embryo-derived TC varies from one mouse strain to another, indicating that some strains are TC-permissive whereas others are relatively TC-nonpermissive. Embryos of a TC-permissive mouse strain (DBA/2J) and a TC-nonpermissive one (C57BL/6J) were transplanted into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice to determine their tumorigenic potential in the absence of functional adaptive and innate immune responses in the hosts. C57BL/6J embryos transplanted to NSG mice gave rise to TC in 31% of cases, whereas the incidence of TC produced from DBA/2J transplanted embryos was 71%. The NSG embryos transplanted to syngeneic hosts gave rise to TC in 67% of cases, allowing the classification of NSG as a TC-permissive strain. A previously reported correlation between teratocarcinoma and splenomegaly was also observed in the NSG mice. The capacity of these tumors to differentiate into the cells and tissues of the normal embryo is mapped through a detailed histological analysis. These data suggest that teratocarcinogenesis, in the absence of host innate and adaptive immunity, is largely determined by the genetic background of the embryo.
将7日龄小鼠胚胎的胚胎部分移植到同基因成年动物的子宫外部位会产生类癌瘤,其可能是良性的[畸胎瘤(T)]或恶性的[畸胎癌(TC)]。胚胎来源的TC发生率因小鼠品系而异,这表明有些品系对TC敏感,而其他品系则相对不敏感。将一个对TC敏感的小鼠品系(DBA/2J)和一个对TC不敏感的品系(C57BL/6J)的胚胎移植到NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ(NSG)小鼠中,以确定它们在宿主缺乏功能性适应性和先天性免疫反应时的致瘤潜力。移植到NSG小鼠中的C57BL/6J胚胎在31%的情况下产生了TC,而移植DBA/2J胚胎产生TC的发生率为71%。移植到同基因宿主中的NSG胚胎在67%的情况下产生了TC,这使得NSG被归类为对TC敏感的品系。在NSG小鼠中还观察到了先前报道的畸胎癌与脾肿大之间的相关性。通过详细的组织学分析绘制了这些肿瘤分化为正常胚胎细胞和组织的能力。这些数据表明,在缺乏宿主先天性和适应性免疫的情况下,畸胎癌发生在很大程度上由胚胎的遗传背景决定。