Transplantation of engineered organoids enables rapid generation of metastatic mouse models of colorectal cancer Academic Article uri icon

Overview

MeSH Major

  • Colorectal Neoplasms
  • Disease Models, Animal
  • Gene Editing
  • Genes, Neoplasm
  • Liver Neoplasms
  • Organ Transplantation

abstract

  • Colorectal cancer (CRC) is a leading cause of death in the developed world, yet facile preclinical models that mimic the natural stages of CRC progression are lacking. Through the orthotopic engraftment of colon organoids we describe a broadly usable immunocompetent CRC model that recapitulates the entire adenoma-adenocarcinoma-metastasis axis in vivo. The engraftment procedure takes less than 5 minutes, shows efficient tumor engraftment in two-thirds of mice, and can be achieved using organoids derived from genetically engineered mouse models (GEMMs), wild-type organoids engineered ex vivo, or from patient-derived human CRC organoids. In this model, we describe the genotype and time-dependent progression of CRCs from adenocarcinoma (6 weeks), to local disseminated disease (11-12 weeks), and spontaneous metastasis (>20 weeks). Further, we use the system to show that loss of dysregulated Wnt signaling is critical for the progression of disseminated CRCs. Thus, our approach provides a fast and flexible means to produce tailored CRC mouse models for genetic studies and pre-clinical investigation.

publication date

  • June 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5462850

Digital Object Identifier (DOI)

  • 10.1038/nbt.3837

PubMed ID

  • 28459450

Additional Document Info

start page

  • 577

end page

  • 582

volume

  • 35

number

  • 6