文章:
斑马鱼癌症:技术的现状和前进的道路
Zebrafish cancer: the state of the art and the path forward
原文发布日期:2013-08-23
DOI: 10.1038/nrc3589
类型: Review Article
开放获取: 否
要点:
- Zebrafish develop cancer that is histologically and genetically similar to that of humans and it can develop spontaneously, after mutagen exposure or through transgenesis.
- Large-scale transgenesis using hundreds to thousands of embryos per day allows for deep functional characterization of genetic abnormalities that have been discovered in human cancer studies, such as The Cancer Genome Atlas.
- Chemical screens have successfully been used in zebrafish embryos to find molecules and pathways that are directly relevant to human malignancy, and drugs from these screens have entered clinical trials in patients.
- Large-scale forward genetic screens offer a unique opportunity to identify cancer phenotypes in an unbiased manner.
- Transparent embryos and adults allows for in vivo visualization of cancer growth and progression at single-cell resolution.
- Xenotransplantation of human cancer cells into zebrafish larvae provides opportunities for personalized cancer screens.
- Major areas of growth in the coming decade include modelling multigenic changes in cancer, epigenetics and the dissection of metastasis.
要点翻译:
- 斑马鱼所患癌症在组织学和遗传学上与人类癌症相似,其癌变可自发产生、继发于诱变剂暴露或通过转基因技术诱发。
- 每日可大规模培育数百至数千个转基因胚胎,借此能对人类癌症研究(如癌症基因组图谱计划)发现的遗传异常进行深入的功能表征。
- 斑马鱼胚胎的化学筛选已成功应用于发现与人类恶性肿瘤直接相关的分子及信号通路,基于这些筛选结果的药物已进入患者临床试验阶段。
- 大规模正向遗传筛选为无偏倚地识别癌症表型提供了独特机遇。
- 胚胎及成鱼的通透性使得在单细胞分辨率下实时观察体内癌症生长与进展成为可能。
- 将人类癌细胞异种移植至斑马鱼幼虫体内,为个性化癌症筛查创造了条件。
- 未来十年的重点发展领域包括:癌症多基因变化建模、表观遗传学研究以及转移机制的解析。
英文摘要:
The zebrafish is a recent addition to animal models of human cancer, and studies using this model are rapidly contributing major insights. Zebrafish develop cancer spontaneously, after mutagen exposure and through transgenesis. The tumours resemble human cancers at the histological, gene expression and genomic levels. The ability to carry out in vivo imaging, chemical and genetic screens, and high-throughput transgenesis offers a unique opportunity to functionally characterize the cancer genome. Moreover, increasingly sophisticated modelling of combinations of genetic and epigenetic alterations will allow the zebrafish to complement what can be achieved in other models, such as mouse and human cell culture systems.
摘要翻译:
斑马鱼是最近加入的人类癌症动物模型之一,利用这一模型进行的研究正在迅速提供重要见解。斑马鱼可在突变暴露和转基因作用下自发发展为癌症。这些肿瘤在组织学、基因表达和基因组水平上均与人类癌症相似。斑马鱼具备体内成像、化学和遗传筛选以及高通量转基因技术的能力,为功能性表征癌症基因组提供了独特机会。此外,斑马鱼对遗传和表观遗传改变的组合进行日益精细的建模,将使其能够补充小鼠和人类细胞培养系统等其他模型所无法实现的成果。
原文链接:
Zebrafish cancer: the state of the art and the path forward