Organoid Models of Human and Mouse Ductal Pancreatic Cancer

Boj, Sylvia F, Hwang, Chang-Il, Baker, Lindsey A, Chio, Iok In Christine, Engle, Dannielle D, Corbo, Vincenzo, Jager, Myrthe, Ponz-Sarvise, Mariano, Tiriac, Hervé, Spector, Mona S, Gracanin, Ana, Oni, Tobiloba, Yu, Kenneth H, van Boxtel, Ruben, Huch, Meritxell, Rivera, Keith D, Wilson, John P, Feigin, Michael E, Öhlund, Daniel, Handly-Santana, Abram, Ardito-Abraham, Christine M, Ludwig, Michael, Elyada, Ela, Alagesan, Brinda, Biffi, Giulia, Yordanov, Georgi N, Delcuze, Bethany, Creighton, Brianna, Wright, Kevin, Park, Youngkyu, Morsink, Folkert H M., Molenaar, I.  Quintus, Borel Rinkes, Inne H, Cuppen, Edwin, Hao, Yuan, Jin, Ying, Nijman, Isaac J, Iacobuzio-Donahue, Christine, Leach, Steven D, Pappin, Darryl J, Hammell, Molly, Klimstra, David S, Basturk, Olca, Hruban, Ralph H, Offerhaus, George Johan, Vries, Robert G J., Clevers, Hans, Tuveson, David A (2015) Organoid Models of Human and Mouse Ductal Pancreatic Cancer. Cell, 160 (1-2). pp. 324-338. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/25557080
DOI: 10.1016/j.cell.2014.12.021

Abstract

Summary 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.

Item Type: Paper
Subjects: organism description > animal > mammal > primates > hominids > human
organism description > model organism
organism description > animal > mammal > rodent > mouse
diseases & disorders > cancer > cancer types > pancreatic cancer
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Program > Signal Transduction
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
CSHL Cancer Center Shared Resources > Mass Spectrometry Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL Cancer Center Shared Resources > Proteomics Service
CSHL labs > Hammell M. lab
CSHL labs > Pappin lab
CSHL labs > Tuveson lab
Watson School > Publications
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date Deposited: 30 Jan 2015 22:01
Last Modified: 04 Nov 2015 15:56
PMCID: PMC4334572
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31154

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