Format

Send to

Choose Destination
Nat Med. 2017 Dec;23(12):1424-1435. doi: 10.1038/nm.4438. Epub 2017 Nov 13.

Human primary liver cancer-derived organoid cultures for disease modeling and drug screening.

Author information

1
The Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge, UK.
2
Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.
3
Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
4
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
5
Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
6
Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
7
Department of Hepato Pancreato Biliary Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
8
Department of Clinical Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK.
9
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.

Abstract

Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

PMID:
29131160
PMCID:
PMC5722201
DOI:
10.1038/nm.4438
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center