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Shifting the focus of zebrafish toward a model of the tumor microenvironment

Cancer cells exist in a complex ecosystem with numerous other cell types in the tumor microenvironment (TME). The composition of this tumor/TME ecosystem will vary at each anatomic site and affects phenotypes such as initiation, metastasis, and drug resistance. A mechanistic understanding of the lar...

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Autores principales: Weiss, Joshua M, Lumaquin-Yin, Dianne, Montal, Emily, Suresh, Shruthy, Leonhardt, Carl S, White, Richard M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9767465/
https://www.ncbi.nlm.nih.gov/pubmed/36538362
http://dx.doi.org/10.7554/eLife.69703
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author Weiss, Joshua M
Lumaquin-Yin, Dianne
Montal, Emily
Suresh, Shruthy
Leonhardt, Carl S
White, Richard M
author_facet Weiss, Joshua M
Lumaquin-Yin, Dianne
Montal, Emily
Suresh, Shruthy
Leonhardt, Carl S
White, Richard M
author_sort Weiss, Joshua M
collection PubMed
description Cancer cells exist in a complex ecosystem with numerous other cell types in the tumor microenvironment (TME). The composition of this tumor/TME ecosystem will vary at each anatomic site and affects phenotypes such as initiation, metastasis, and drug resistance. A mechanistic understanding of the large number of cell-cell interactions between tumor and TME requires models that allow us to both characterize as well as genetically perturb this complexity. Zebrafish are a model system optimized for this problem, because of the large number of existing cell-type-specific drivers that can label nearly any cell in the TME. These include stromal cells, immune cells, and tissue resident normal cells. These cell-type-specific promoters/enhancers can be used to drive fluorophores to facilitate imaging and also CRISPR cassettes to facilitate perturbations. A major advantage of the zebrafish is the ease by which large numbers of TME cell types can be studied at once, within the same animal. While these features make the zebrafish well suited to investigate the TME, the model has important limitations, which we also discuss. In this review, we describe the existing toolset for studying the TME using zebrafish models of cancer and highlight unique biological insights that can be gained by leveraging this powerful resource.
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spelling pubmed-97674652022-12-21 Shifting the focus of zebrafish toward a model of the tumor microenvironment Weiss, Joshua M Lumaquin-Yin, Dianne Montal, Emily Suresh, Shruthy Leonhardt, Carl S White, Richard M eLife Cancer Biology Cancer cells exist in a complex ecosystem with numerous other cell types in the tumor microenvironment (TME). The composition of this tumor/TME ecosystem will vary at each anatomic site and affects phenotypes such as initiation, metastasis, and drug resistance. A mechanistic understanding of the large number of cell-cell interactions between tumor and TME requires models that allow us to both characterize as well as genetically perturb this complexity. Zebrafish are a model system optimized for this problem, because of the large number of existing cell-type-specific drivers that can label nearly any cell in the TME. These include stromal cells, immune cells, and tissue resident normal cells. These cell-type-specific promoters/enhancers can be used to drive fluorophores to facilitate imaging and also CRISPR cassettes to facilitate perturbations. A major advantage of the zebrafish is the ease by which large numbers of TME cell types can be studied at once, within the same animal. While these features make the zebrafish well suited to investigate the TME, the model has important limitations, which we also discuss. In this review, we describe the existing toolset for studying the TME using zebrafish models of cancer and highlight unique biological insights that can be gained by leveraging this powerful resource. eLife Sciences Publications, Ltd 2022-12-20 /pmc/articles/PMC9767465/ /pubmed/36538362 http://dx.doi.org/10.7554/eLife.69703 Text en © 2022, Weiss, Lumaquin-Yin, Montal et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Weiss, Joshua M
Lumaquin-Yin, Dianne
Montal, Emily
Suresh, Shruthy
Leonhardt, Carl S
White, Richard M
Shifting the focus of zebrafish toward a model of the tumor microenvironment
title Shifting the focus of zebrafish toward a model of the tumor microenvironment
title_full Shifting the focus of zebrafish toward a model of the tumor microenvironment
title_fullStr Shifting the focus of zebrafish toward a model of the tumor microenvironment
title_full_unstemmed Shifting the focus of zebrafish toward a model of the tumor microenvironment
title_short Shifting the focus of zebrafish toward a model of the tumor microenvironment
title_sort shifting the focus of zebrafish toward a model of the tumor microenvironment
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9767465/
https://www.ncbi.nlm.nih.gov/pubmed/36538362
http://dx.doi.org/10.7554/eLife.69703
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