Establishment of an in vivo model for pediatric Ewing tumors by transplantation into NOD/scid mice
Establishment of an in vivo model for pediatric Ewing tumors by transplantation into NOD/scid mice
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DOI：
10.1203/00006450-200103000-00006
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发表时间：
2001-03-01
影响因子：
3.6
通讯作者：
Dockhorn-Dworniczak, B
中科院分区：
文献类型：
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作者：
Vormoor, J;Baersch, G;Dockhorn-Dworniczak, B
尤文肿瘤是一组临床异质性的儿童肉瘤，代表了理解实体肿瘤生物学的范例，因为它们是第一组在分子水平上描述了染色体易位的肉瘤。然而。肿瘤的生物组织，特别是控制原始肿瘤干细胞增殖、分化和转移的过程，人们知之甚少。因此，为了建立具有生物学意义的体内模型，通过静脉注射将来自三个患者的五个不同的尤文肿瘤细胞系和原代肿瘤细胞移植到免疫缺陷小鼠体内。NOD/SCID小鼠携带复杂的免疫缺陷，因此几乎完全缺乏排斥人类细胞的能力，被用作受体。总的来说。移植VH-、WE-68、CADO-ES1、TC-71和RM-82细胞的小鼠26只(50%)，移植原代肿瘤细胞的小鼠4只(40%)。此外，没有在体外生长的原代细胞在小鼠体内增殖。转移方式与肺(62%)、骨髓(30%)和骨(23%)转移频繁的患者相似。通过有限稀释实验，估计在3×10(5)VH-细胞中植入单位的频率为1个尤文肿瘤起始细胞。这些数据表明，我们已经能够建立一个体内模型，概括了人类尤文肿瘤生长和发展的许多方面。这一模型首次为鉴定和鉴定体内原始克隆性实体瘤干细胞提供了机会。因此，该模型将有助于研究肿瘤细胞生物学的许多方面，包括器官选择性转移和肿瘤血管生成。
Ewing tumors are a clinically heterogeneous group of childhood sarcomas that represent a paradigm for understanding solid tumor biology, as they are the first group of sarcomas for which a chromosome translocation has been characterized at the molecular level. However. the biologic organization of the tumor, especially the processes that govern proliferation, differentiation, and metastasis of primitive tumor stem cells is poorly understood. Therefore, to develop a biologically relevant in vivo model, five different Ewing tumor cell lines and primary tumor cells from three patients were transplanted into immune-deficient mice via intravenous injection. NOD/scid mice that carry a complex immune deficiency and thus nearly completely lack the ability to reject human cells were used as recipients. Overall. 26 of 52 mice (50%) transplanted with VH-64, WE-68, CADO-ES1, TC-71, and RM-82 cells and 4 of 10 mice (40%) transplanted with primary tumor cells engrafted. Moreover, primary cells that did not grow in vitro proliferated in mice. The pattern of metastasis was similar to that in patients with frequent metastases in lungs (62%), bone marrow (30%), and bone (23%). Using limiting dilution experiments, the frequency of the engraftment unit was estimated at 1 Ewing tumor-initiating cell in 3 x 10(5) VH-64 cells. These data demonstrate that we have been able to establish an in vivo model that recapitulates many aspects of growth and progression of human Ewing tumors. For the first time, this model provides the opportunity to identify and characterize primitive in vivo clonogenic solid tumor stem cells. This model will, therefore, be instrumental in studying many aspects of tumor cell biology, including organ-selective metastasis and tumor angiogenesis.