Zebrafish Model of Neuroblastoma Metastasis.

Zebrafish Model of Neuroblastoma Metastasis.
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DOI:
10.3791/62416
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发表时间:
2021-03-14
期刊:
Journal of visualized experiments : JoVE
影响因子:
--
通讯作者:
Zhu S
Zhu S
中科院分区:
其他
文献类型:
--
作者:
Her ZP;Yeo KS;Howe C;Levee T;Zhu S

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斑马鱼已成为研究人类疾病,特别是癌症的重要动物模型。沿着在斑马鱼建模中应用的强大的转基因和基因组编辑技术,易于维护,高产率和强大的活体成像共同使斑马鱼成为研究体内转移和该过程背后的细胞和分子基础的有价值的模型系统。第一个转移的斑马鱼神经母细胞瘤(NB)模型是通过在多巴胺-β-羟化酶(dβh)启动子的控制下过表达两种癌基因MYCN和LMO 1而开发的。MYCN和LMO 1共表达可导致神经母细胞瘤发生的潜伏期缩短、潜伏期增加,并加速肿瘤细胞的远处转移。这种新模型可靠地重申了人类转移性NB的许多关键特征,包括涉及临床相关和转移相关的遗传改变;体内转移的自然和自发发展;以及转移的保守位点。因此,斑马鱼模型在研究体内肿瘤转移的复杂过程中具有独特的优势。
Zebrafish has emerged as an important animal model to study human diseases, especially cancer. Along with the robust transgenic and genome editing technologies applied in zebrafish modeling, the ease of maintenance, high-yield productivity, and powerful live imaging altogether make the zebrafish a valuable model system to study metastasis and cellular and molecular bases underlying this process in vivo. The first zebrafish neuroblastoma (NB) model of metastasis was developed by overexpressing two oncogenes, MYCN and LMO1, under control of the dopamine-beta-hydroxylase (dβh) promoter. Co-overexpressed MYCN and LMO1 led to the reduced latency and increased penetrance of neuroblastomagenesis, as well as accelerated distant metastasis of tumor cells. This new model reliably reiterates many key features of human metastatic NB, including involvement of clinically relevant and metastasis-associated genetic alterations; natural and spontaneous development of metastasis in vivo; and conserved sites of metastases. Therefore, the zebrafish model possesses unique advantages to dissect the complex process of tumor metastasis in vivo.
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