PUBLICATION

Patient-derived Heterogeneous Xenograft Model of Pancreatic Cancer Using Zebrafish Larvae as Hosts for Comparative Drug Assessment

Authors
Wang, L., Chen, H., Fei, F., He, X., Sun, S., Lv, K., Yu, B., Long, J., Wang, X.
ID
ZDB-PUB-190521-5
Date
2019
Source
Journal of visualized experiments : JoVE   (146): (Journal)
Registered Authors
Wang, Xu
Keywords
none
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Heterografts*
  • Humans
  • Larva
  • Mice
  • Neoplasm Transplantation*/methods
  • Pancreatic Neoplasms*
  • Tumor Microenvironment
  • Xenograft Model Antitumor Assays/methods*
  • Zebrafish
PubMed
31107449 Full text @ J. Vis. Exp.
Abstract
Patient-derived tumor xenograft (PDX) and cell-derived tumor xenograft (CDX) are important techniques for preclinical assessment, medication guidance and basic cancer researches. Generations of PDX models in traditional host mice are time-consuming and only working for a small proportion of samples. Recently, zebrafish PDX (zPDX) has emerged as a unique host system, with the characteristics of small-scale and high efficiency. Here, we describe an optimized methodology for generating a dual fluorescence-labeled tumor xenograft model for comparative chemotherapy assessment in zPDX models. Tumor cells and fibroblasts were enriched from freshly-harvested or frozen pancreatic cancer tissue at different culture conditions. Both cell groups were labeled by lentivirus expressing green or red fluorescent proteins, as well as an anti-apoptosis gene BCL2L1. The transfected cells were pre-mixed and co-injected into the 2 dpf larval zebrafish that were then bred in modified E3 medium at 32 °C. The xenograft models were treated by chemotherapy drugs and/or BCL2L1 inhibitor, and the viabilities of both tumor cells and fibroblasts were investigated simultaneously. In summary, this protocol allows researchers to quickly generate a large amount of zPDX models with a heterogeneous tumor microenvironment and provides a longer observation window and a more precise quantitation in assessing the efficiency of drug candidates.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes