Benefits of Zebrafish Xenograft Models in Cancer Research

Abstract

As a promising in vivo tool for cancer research, zebrafish have been widely applied in various tumor studies. The zebrafish xenograft model is a low-cost, high-throughput tool for cancer research that can be established quickly and requires only a small sample size, which makes it favorite among researchers. Zebrafish patient-derived xenograft (zPDX) models provide promising evidence for short-term clinical treatment. In this review, we discuss the characteristics and advantages of zebrafish, such as their transparent and translucent features, the use of vascular fluorescence imaging, the establishment of metastatic and intracranial orthotopic models, individual pharmacokinetics measurements, and tumor microenvironment. Furthermore, we introduce how these characteristics and advantages are applied other in tumor studies. Finally, we discuss the future direction of the use of zebrafish in tumor studies and provide new ideas for the application of it.

TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion

“…We have used zebrafish ( Danio rerio ) embryos as an alternative to vertebrate models. This model is becoming frequently used in cancer research [ 14 , 36 , 37 , 58 ], mostly due to the fact that the transparent embryos enable high-resolution imaging of implanted cancer cells on a single level and that have not yet developed an immune system, thus the additional immunosuppression is not needed. Zebrafish embryos are also transparent with developed brain structures, which mimic the brain microenvironment in humans, enabling high-resolution imaging of implanted cancer.…”

Inhibition of Metastatic Uveal Melanoma Cell Proliferation by the Histone Deacetylase 6 Inhibitor, Ricolinostat, is Linked to Altered Microphthalmia-associated Transcription Factor and Phospho-ERK Expression

“…This is not surprising given the timeframe of the experiment, and a low burden in the average number of disseminated cells to the caudal vein plexus three days post transplantation in the vehicle controls. It would be worthwhile to perform follow-up studies to evaluate the efficacy of ACY-1215 on tumor metastasis, with long-term treatment regimens and in patientderived samples in vivo in larvae and/or in adult zebrafish [51][52][53][54].…”

Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules

“…In 1981 [ 29 ], the idea to use the zebrafish as a novel vertebrate model organism to study human diseases and test innovative therapeutic molecules/strategies was first proposed. There are several reasons for its use in biomedical research [ 30 , 31 ] ( Figure 1 ). First, zebrafish has a high fecundity, so many animals can be produced in a short time; moreover, both embryos and adults have a small size, so little space is needed for housing.…”

“…Interestingly, improvements were also made regarding the origin of the cells to be xenotransplanted. Initially, human cancer cell lines were used, leading to the so-called cell-line-derived xenograft (CDX) models [ 30 ]. Human cancer cell lines are easy to obtain and are very suitable for replication experiments.…”

“…However, continuous in vitro passage may alter their phenotypic/genetic pattern, moving them away from the original tumor characteristics. To circumvent this aspect, patient-derived tumor cells have been used to generate xenograft zebrafish models (Patient-Derived Tumor Xenograft (PDX) model) [ 30 ]. A major advantage of PDX is that only a few patient-derived cells are needed to generate PDX in zebrafish, as compared to other animal models, such as rodents, which are often difficult to use for this purpose.…”