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


Authors: Weiss, J. M.; Lumaquin-Yin, D.; Montal, E.; Suresh, S.; Leonhardt, C. S.; White, R. M.
Review Title: Shifting the focus of zebrafish toward a model of the tumor microenvironment
Abstract: 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 resi-dent 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. © Weiss, Lumaquin-Yin, Montal et al.
Keywords: treatment outcome; promoter region; genetics; review; nonhuman; neoplasm; neoplasms; t lymphocyte; phenotype; animal; animals; cell function; melanoma; metastasis; immune system; gene expression; biological model; models, biological; confocal microscopy; image analysis; melanocyte; germ cell; astrocyte; transcription factor; pathology; keratinocyte; b lymphocyte; carcinogenesis; endothelium cell; germ line; neutrophil; immunotherapy; xenograft; epigenetics; cancer cell; tumor cell; osteoclast; macrophage; doxycycline; stroma cell; endocrine cell; cell interaction; cell communication; b raf kinase; bioluminescence; immunocompetent cell; zebra fish; zebrafish; cell transplantation; osteoblast; rna sequence; nitroreductase; enhancer region; tumor microenvironment; adipocyte; microglia; fat droplet; ecosystem; mitogen activated protein kinase kinase inhibitor; epifluorescence microscopy; transgenic zebrafish; human; clustered regularly interspaced short palindromic repeat; gene editing; smooth muscle cell
Journal Title: eLife
Volume: 11
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd.  
Date Published: 2022-12-20
Start Page: e69703
Language: English
DOI: 10.7554/elife.69703
PUBMED: 36538362
PROVIDER: scopus
PMCID: PMC9767465
DOI/URL:
Notes: Review -- Export Date: 1 February 2023 -- Source: Scopus
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  1. Richard Mark White
    68 White
  2. Emily Dina Montal
    14 Montal
  3. Shruthy Suresh
    8 Suresh