Cancer Metabolism Laboratory, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Adv Exp Med Biol. 2020;1219:413-428. doi: 10.1007/978-3-030-34025-4_22.
The zebrafish larvae have emerged as a powerful model for studying tumorigenesis in vivo, with remarkable conservation with mammals in genetics, molecular and cell biology. Zebrafish tumor models bear the significant advantages of optical clarity in comparison to that in the mammalian models, allowing noninvasive investigation of the tumor cell and its microenvironment at single-cell resolution. Here we review recent progressions in the field of zebrafish models of solid tumor diseases in two main categories: the genetically engineered tumor models in which all cells in the tumor microenvironment are zebrafish cells, and xenograft tumor models in which the tumor microenvironment is composed of zebrafish cells and cells from other species. Notably, the zebrafish patient-derived xenograft (zPDX) models can be used for personalized drug assessment on primary tumor biopsies, including the pancreatic cancer. For the future studies, a series of high throughput drug screenings on the library of transgenic zebrafish models of solid tumor are expected to provide systematic database of oncogenic mutation, cell-of-origin, and leading compounds; and the humanization of zebrafish in genetics and cellular composition will make it more practical hosts for zPDX modeling. Together, zebrafish tumor model systems are unique and convenient in vivo platforms, with great potential to serve as valuable tools for cancer researches.
斑马鱼幼虫已成为研究体内肿瘤发生的强大模型，在遗传学、分子和细胞生物学方面与哺乳动物有显著的相似性。与哺乳动物模型相比，斑马鱼肿瘤模型具有显著的光学透明优势，允许以单细胞分辨率对肿瘤细胞及其微环境进行非侵入性研究。在这里，我们综述了两种主要类别中斑马鱼实体瘤模型领域的最新进展：遗传工程肿瘤模型，其中肿瘤微环境中的所有细胞均为斑马鱼细胞；以及异种移植肿瘤模型，其中肿瘤微环境由斑马鱼细胞和来自其他物种的细胞组成。值得注意的是，斑马鱼患者衍生的异种移植（zPDX）模型可用于对原发性肿瘤活检进行个性化药物评估，包括胰腺癌。未来的研究预计将对实体瘤的转基因斑马鱼模型文库进行一系列高通量药物筛选，从而提供致癌突变、起源细胞和先导化合物的系统数据库；并通过遗传学和细胞组成实现斑马鱼的人类化，将其作为 zPDX 建模更实用的宿主。总之，斑马鱼肿瘤模型系统是独特且方便的体内平台，具有成为癌症研究有价值工具的巨大潜力。
