甲状腺间变性癌
斑马鱼
肿瘤微环境
癌症研究
体内
癌变
甲状腺癌
生物
癌症
细胞生长
医学
内科学
肿瘤细胞
生物化学
遗传学
生物技术
基因
作者
Cassia Michael,Juliana Moreira Mendonça-Gomes,Clinton Walton DePaolo,Antonio Di Cristofano,Sofía de Oliveira
出处
期刊:Endocrine-related Cancer
[Bioscientifica]
日期:2024-04-01
摘要
Anaplastic thyroid cancer (ATC) is of the most aggressive thyroid cancer. While ATC is rare it accounts for a disproportionately high number of thyroid cancer-related deaths. Here we developed an ATC xenotransplant model in zebrafish larvae, where we can study tumorigenesis and therapeutic response in vivo. Using both mouse (T4888M) and human (C643) derived fluorescently labeled ATC cell lines we show these cell lines display different engraftment rates, mass volume, proliferation, cell death, angiogenic potential and neutrophil and macrophage recruitment and infiltration. Next, using a PIP-FUCCI reporter to track proliferation in-vivo we observed cells in each phase of the cell cycle. Additionally, we performed long-term non-invasive intravital microscopy over 48 hours to understand cellular dynamics in the tumor microenvironment at the single cell level. Lastly, we tested two drug treatments, AZD2014 and a combination therapy of dabrafenib and trametinib to show our model could be used as an effective screening platform for new therapeutic compounds for ATC. Altogether, we show that zebrafish xenotransplants make a great model to study thyroid carcinogenesis and the tumor microenvironment, while also being a suitable model to test new therapeutics in vivo.
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