In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma

In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma
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DOI:
10.1016/j.ccr.2012.03.043
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发表时间:
2012-05-15
期刊:
影响因子:
50.3
通讯作者:
Langenau, David M.
Langenau, David M.
中科院分区:
医学1区
文献类型:
--
作者:
Ignatius, Myron S.;Chen, Eleanor;Langenau, David M.

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胚胎性横纹肌肉瘤(ERMS)是一种儿童侵袭性肌肉肉瘤。在这里,我们展示了ERMS的传播潜力仅限于myf5+细胞,并且可以在活的荧光转基因斑马鱼中观察到。在肿瘤生长的早期,myf5+erms细胞与正常肌肉纤维相邻。通过晚期ERMS,myf5+细胞被重组成与分化的肿瘤细胞分开的不同区域。晚期ERMS的时间推移成像显示,myf5+细胞只有在高迁移的mygenin+erms细胞种植后才能填充新形成的肿瘤。此外,mygenin+erms细胞可以进入血管系统,而myf5+erms增殖细胞不能。我们的数据表明,非肿瘤增殖细胞可能在癌症进展和促进转移中起着重要的支持作用。
Embryonal rhabdomyosarcoma (ERMS) is an aggressive pediatric sarcoma of muscle. Here, we show that ERMS-propagating potential is confined to myf5+ cells and can be visualized in live, fluorescent transgenic zebrafish. During early tumor growth, myf5+ ERMS cells reside adjacent normal muscle fibers. By late-stage ERMS, myf5+ cells are reorganized into distinct regions separated from differentiated tumor cells. Time-lapse imaging of late-stage ERMS revealed that myf5+ cells populate newly formed tumor only after seeding by highly migratory myogenin+ ERMS cells. Moreover, myogenin+ ERMS cells can enter the vasculature, whereas myf5+ ERMS-propagating cells do not. Our data suggest that non-tumor-propagating cells likely have important supportive roles in cancer progression and facilitate metastasis.