title: Organoid models of human and mouse ductal pancreatic cancer.
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.
authors.affiliation: 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.
authors.forename: Sylvia F
authors.initials: SF
authors.lastname: Boj
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Chang-Il
authors.initials: CI
authors.lastname: Hwang
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Baker
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Iok In Christine
authors.initials: II
authors.lastname: Chio
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Dannielle D
authors.initials: DD
authors.lastname: Engle
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Corbo
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands.
authors.forename: Myrthe
authors.initials: M
authors.lastname: Jager
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Mariano
authors.initials: M
authors.lastname: Ponz-Sarvise
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Hervé
authors.initials: H
authors.lastname: Tiriac
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Mona S
authors.initials: MS
authors.lastname: Spector
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Gracanin
authors.affiliation: 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.
authors.forename: Tobiloba
authors.initials: T
authors.lastname: Oni
authors.affiliation: 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.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Yu
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: van Boxtel
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Huch
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Rivera
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Wilson
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Feigin
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Öhlund
authors.affiliation: 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.
authors.forename: Abram
authors.initials: A
authors.lastname: Handly-Santana
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Ardito-Abraham
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Ela
authors.initials: E
authors.lastname: Elyada
authors.affiliation: 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.
authors.forename: Brinda
authors.initials: B
authors.lastname: Alagesan
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Biffi
authors.affiliation: 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.
authors.forename: Georgi N
authors.initials: GN
authors.lastname: Yordanov
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Bethany
authors.initials: B
authors.lastname: Delcuze
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Creighton
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wright
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Youngkyu
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Folkert H M
authors.initials: FH
authors.lastname: Morsink
authors.affiliation: Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: I Quintus
authors.initials: IQ
authors.lastname: Molenaar
authors.affiliation: Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Inne H
authors.initials: IH
authors.lastname: Borel Rinkes
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands.
authors.forename: Isaac J
authors.initials: IJ
authors.lastname: Nijman
authors.affiliation: Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Iacobuzio-Donahue
authors.affiliation: Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Leach
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Pappin
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Hammell
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Olca
authors.initials: O
authors.lastname: Basturk
authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: George Johan
authors.initials: GJ
authors.lastname: Offerhaus
authors.affiliation: 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.
authors.forename: Robert G J
authors.initials: RG
authors.lastname: Vries
authors.affiliation: 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.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: 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.
authors.forename: David A
authors.initials: DA
authors.lastname: Tuveson
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008954:Models, Biological; D009924:Organ Culture Techniques; D009940:Organoids / Q000473:pathology*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology*