A zebrafish xenotransplant model of anaplastic thyroid cancer to study tumor microenvironment and innate immune cell interactions in vivo

in Endocrine-Related Cancer
Authors:
Cassia Michael Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA

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Juliana Moreira Mendonça-Gomes Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA

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Clinton Walton DePaolo Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA

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Antonio Di Cristofano Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA
Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, New York, USA
Montefiore-Einstein Comprehensive Cancer Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
Cancer Dormancy Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, New York, USA

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https://orcid.org/0000-0003-2537-3228
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Sofia de Oliveira Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA
Montefiore-Einstein Comprehensive Cancer Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
Cancer Dormancy Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, New York, USA
Department of Medicine (Hepatology), Albert Einstein College of Medicine, Bronx, New York, USA
Marion Bessin Liver Research Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA

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https://orcid.org/0000-0003-0893-111X

Correspondence should be addressed to S De Oliveira or A Di Cristofano: sofia.deoliveira@einsteinmed.edu or antonio.dicristofano@einsteinmed.edu
DOI:
https://doi.org/10.1530/ERC-23-0195
Volume/Issue:
Volume 31: Issue 7
Article Type:
Research Article
Article ID:
e230195
Online Publication Date:
15 May 2024
Copyright:
© the author(s) 2024
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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 h 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.

Supplementary Materials

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2024
Article ID:
e230195
Received Date:
22 Jun 2023
Accepted Date:
23 Apr 2024
Print Publication Date:
01 Jul 2024
Online Publication Date:
15 May 2024
Keywords:
microscopy; neutrophils; tumor microenvironment; xenotransplant; zebrafish

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