| Literature DB >> 25557080 |
Sylvia F Boj1, Chang-Il Hwang2, Lindsey A Baker2, Iok In Christine Chio2, Dannielle D Engle2, Vincenzo Corbo2, Myrthe Jager3, Mariano Ponz-Sarvise2, Hervé Tiriac2, Mona S Spector2, Ana Gracanin1, Tobiloba Oni4, Kenneth H Yu5, Ruben van Boxtel3, Meritxell Huch3, Keith D Rivera6, John P Wilson6, Michael E Feigin2, Daniel Öhlund2, Abram Handly-Santana7, Christine M Ardito-Abraham2, Michael Ludwig2, Ela Elyada2, Brinda Alagesan8, Giulia Biffi2, Georgi N Yordanov7, Bethany Delcuze2, Brianna Creighton2, Kevin Wright2, Youngkyu Park2, Folkert H M Morsink9, I Quintus Molenaar10, Inne H Borel Rinkes10, Edwin Cuppen3, Yuan Hao6, Ying Jin6, Isaac J Nijman3, Christine Iacobuzio-Donahue11, Steven D Leach11, Darryl J Pappin6, Molly Hammell6, David S Klimstra12, Olca Basturk12, Ralph H Hruban13, George Johan Offerhaus9, Robert G J Vries1, Hans Clevers14, David A Tuveson15.
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.Entities:
Mesh：
Year: 2014 PMID： 25557080 PMCID： PMC4334572 DOI： 10.1016/j.cell.2014.12.021
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582