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Cell. 2015 Jan 15;160(1-2):324-38. doi: 10.1016/j.cell.2014.12.021. Epub 2014 Dec 31.

Organoid models of human and mouse ductal pancreatic cancer.

Author information

1
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands; foundation Hubrecht Organoid Technology (HUB), 3584 CT Utrecht, the Netherlands.
2
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
3
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands.
4
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA; Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY 11794, USA.
5
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA; Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Medical College at Cornell University, New York, NY 10065, USA.
6
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
7
Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA; Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
8
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA; Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
9
Department of Pathology, University Medical Centre Utrecht, 3584 CX Utrecht, the Netherlands.
10
Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
11
Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
12
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
13
The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
14
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu.
15
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA; Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: dtuveson@cshl.edu.

Abstract

Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.

PMID:
25557080
PMCID:
PMC4334572
DOI:
10.1016/j.cell.2014.12.021
[Indexed for MEDLINE]
Free PMC Article
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