Modeling of Solid-Tumor Microenvironment in Zebrafish (Danio Rerio) Larvae

Abstract

The zebrafish larvae have emerged as a powerful model for studying tumorigenesis in vivo, with remarkable conservation with mammals in genetics, molecular and cell biology. Zebrafish tumor models bear the significant advantages of optical clarity in comparison to that in the mammalian models, allowing noninvasive investigation of the tumor cell and its microenvironment at single-cell resolution. Here we review recent progressions in the field of zebrafish models of solid tumor diseases in two main categories: the genetically engineered tumor models in which all cells in the tumor microenvironment are zebrafish cells, and xenograft tumor models in which the tumor microenvironment is composed of zebrafish cells and cells from other species. Notably, the zebrafish patient-derived xenograft (zPDX) models can be used for personalized drug assessment on primary tumor biopsies, including the pancreatic cancer. For the future studies, a series of high throughput drug screenings on the library of transgenic zebrafish models of solid tumor are expected to provide systematic database of oncogenic mutation, cell-of-origin, and leading compounds; and the humanization of zebrafish in genetics and cellular composition will make it more practical hosts for zPDX modeling. Together, zebrafish tumor model systems are unique and convenient in vivo platforms, with great potential to serve as valuable tools for cancer researches.

Keywords: Animal model; Chimeric antigen receptor (CAR) T-cells; Transgenesis; Tumor microenvironment; Xenograft; Zebrafish.