PUBLICATION
A zebrafish xenotransplant model of anaplastic thyroid cancer to study the tumor microenvironment and innate immune cell interactions in vivo
- Authors
- Michael, C., Mendonça-Gomes, J.M., DePaolo, C.W., Di Cristofano, A., De Oliveira, S.
- ID
- ZDB-PUB-240425-8
- Date
- 2024
- Source
- Endocrine-related cancer 31(7): (Unpublished)
- Registered Authors
- de Oliveira, Sofia
- Keywords
- none
- MeSH Terms
-
- Pyrimidinones/pharmacology
- Pyrimidinones/therapeutic use
- Imidazoles/pharmacology
- Imidazoles/therapeutic use
- Animals
- Pyridones/pharmacology
- Pyridones/therapeutic use
- Thyroid Neoplasms/immunology
- Thyroid Neoplasms/pathology
- Zebrafish*
- Mice
- Tumor Microenvironment*/immunology
- Immunity, Innate
- Disease Models, Animal
- Humans
- Cell Line, Tumor
- Thyroid Carcinoma, Anaplastic*/immunology
- Thyroid Carcinoma, Anaplastic*/pathology
- PubMed
- 38657656 Full text @ Endocr. Relat. Cancer
Citation
Michael, C., Mendonça-Gomes, J.M., DePaolo, C.W., Di Cristofano, A., De Oliveira, S. (2024) A zebrafish xenotransplant model of anaplastic thyroid cancer to study the tumor microenvironment and innate immune cell interactions in vivo. Endocrine-related cancer. 31(7):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping