Transplantation of engineered organoids enables rapid generation of metastatic mouse models of colorectal cancer.

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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

O'Rourke KP,Loizou E,Livshits G,Schatoff EM,Baslan T,Manchado E,Simon J,Romesser PB,Leach B,Han T,Pauli C,Beltran H,Rubin MA,Dow LE,Lowe SW

doi

10.1038/nbt.3837

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

577-582

issue

6

eissn

1087-0156

issn

1546-1696

pii

nbt.3837

journal_volume

35

pub_type

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