Zebrafish as a Neuroblastoma Model: Progress Made, Promise for the Future

Abstract

For nearly a decade, researchers in the field of pediatric oncology have been using zebrafish as a model for understanding the contributions of genetic alternations to the pathogenesis of neuroblastoma (NB), and exploring the molecular and cellular mechanisms that underlie neuroblastoma initiation and metastasis. In this review, we will enumerate and illustrate the key advantages of using the zebrafish model in NB research, which allows researchers to: monitor tumor development in real-time; robustly manipulate gene expression (either transiently or stably); rapidly evaluate the cooperative interactions of multiple genetic alterations to disease pathogenesis; and provide a highly efficient and low-cost methodology to screen for effective pharmaceutical interventions (both alone and in combination with one another). This review will then list some of the common challenges of using the zebrafish model and provide strategies for overcoming these difficulties. We have also included visual diagram and figures to illustrate the workflow of cancer model development in zebrafish and provide a summary comparison of commonly used animal models in cancer research, as well as key findings of cooperative contributions between MYCN and diverse singling pathways in NB pathogenesis.

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma

“…Tumors arising in Dbh-iCre;CAG-MYC closely mimic the histopathological and molecular features of human neuroblastoma, and respond to the FDA-approved immunotherapy and targeted therapy for neuroblastoma treatment. So far, all successful genetic neuroblastoma models have been based on the activation of MYC in either Th-or Dbh-positive cells [22][23][24][25][26][27][28] . Unexpectedly, we found that crossing of Dbh-Cre with CAG-MYC was unable to initiate tumorigenesis, suggesting that the Cre with improved coding sequences (iCre) has a better activity to drive c-MYC-mediated tumorigenesis.…”

“…A recent pan-neuroblastoma genomic analysis further confirmed previous studies showing that the most frequently altered genes were MYCN (19%, primarily amplification), TERT (17%; structural variations), SHANK2 (13%; structural variations), PTPRD (11%; structural variations and focal deletions), ALK (10%; somatic nucleotide variations and structural variations), and ATRX (8%, multiple mutation types) 11 . Genetically engineered mouse and zebrafish models of neuroblastoma have validated MYCN as a key oncogenic driver of neuroblastoma tumorigenesis, which can be promoted by other oncogenes such as ALK, LIN28B and LMO1 [22][23][24][25][26][27][28][29][30][31] (Table 1). These genetic models have served as valuable tools to explore and test targeted therapies and immunotherapies [32][33][34][35][36][37][38][39][40] , helping to advance the clinical trials of ALK inhibitors and CAR therapies [41][42][43][44][45] , as well as approval of DFMO by the FDA for adult and pediatric patients with highrisk neuroblastoma who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy 46 .…”

Danio rerio: A Sustainable Model for Monitoring Pollutants in Aquatic Environments

“…Unit Permissible Limits Optimum Limits In toxicological studies, especially in order to determine the toxic levels of environmental pollutants, parameters close to the natural environment of zebrafish should be provided in the laboratory environment. In this context, water quality parameters come to the fore (Table 1) [20][21][22][23]. The zebrafish is found in rivers, streams, canals, and rice fields in India, Pakistan, Bangladesh, Nepal, Myanmar, and Bhutan [22].…”

“…The zebrafish is found in rivers, streams, canals, and rice fields in India, Pakistan, Bangladesh, Nepal, Myanmar, and Bhutan [22]. Wild zebrafish distribution includes Brazil, Colombia, Malaysia, Sri Lanka, Thailand, and the United States [21,23]. Native zebrafish is found in more than 3000 institutions in more than 100 countries and is a popular aquarium fish [22,24].…”

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

“…In recent decades, numerous disease models have been established using zebrafish larvae to study developmental processes, such as hematology [ 194 , 195 ], and pathogenic processes in cancer [ 196 ] and infectious diseases [ 197 ]. Zebrafish models have contributed to uncovering pathogenic mechanisms and to the discovery and efficacy screening of innovative drugs [ 198 , 199 ].…”