Organoid models of human and mouse ductal pancreatic cancer

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

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

1480 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)324-38
Aantal pagina's15
Nummer van het tijdschrift1-2
StatusGepubliceerd - 15 jan. 2015


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