Journal
CELL
Volume 160, Issue 1-2, Pages 324-338Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.12.021
Keywords
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Categories
Funding
- Cancer Center Support Grant [5P30CA045508]
- Cold SpringHarbor Laboratory Association
- Carcinoid Foundation
- PCUK
- David Rubinstein Center for Pancreatic Cancer Research at MSKCC
- Stand Up to Cancer/KWF
- STARR foundation [I7-A718]
- DOD [W81XWH-13-PRCRP-IA]
- Sol Goldman Pancreatic Cancer Research Center
- Italian Ministry of Health [FIRB-RBAP10AHJ]
- Sociedad Espanola de Oncologia Medica (SEOM)
- Louis Morin Charitable Trust
- Swedish Research Council [537-2013-7277]
- Kempe Foundations [JCK-1301]
- Swedish Society of Medicine [S-326921, SLS-250831]
- Damon Runyon Cancer Research Foundation [DRG-2165-13]
- Human Frontiers Science Program [LT000403/2014]
- Weizmann Institute of Science Women in Science Award
- American Cancer Society [PF-13-317-01-CSM]
- Hearst Foundation
- NIH [5P30CA45508-26, 5P50CA101955-07, 1U10CA18094401, 5U01CA168409-3, 1R01CA190092-01, CA62924, CA134292, 5T32CA148056, CA101955 UAB/UMN SPORE]
- KWF/PF-HUBR [2007-3956]
- GenomiCs.nl
- CancerGenomics.nl (NWO Gravitation) program
- [EU/232814StemCellMark]
- Pancreatic Cancer UK [2010 Grant - Tuveson, PCUK-2011 Grant - Tuveson] Funding Source: researchfish
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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.
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