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Cold Spring Harbor Laboratory, Lustgarten Foundation Pancreatic Cancer Research Laboratory
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조회 4312  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Organoid Models of Human and Mouse Ductal Pancreatic Cancer

Sylvia F. Boj,1,2,14 Chang-Il Hwang,3,4,14 Lindsey A. Baker,3,4,14 Iok In Christine Chio,3,4,14 Dannielle D. Engle,3,4,14 Vincenzo Corbo,3,4,14 Myrthe Jager,1,14 Mariano Ponz-Sarvise,3,4 Hervé Tiriac,3,4 Mona S. Spector,3,4 Ana Gracanin,1,2 Tobiloba Oni,3,4,5 Kenneth H. Yu,3,4,6,7 Ruben van Boxtel,1 Meritxell Huch,1,15 Keith D. Rivera,3 John P. Wilson,3 Michael E. Feigin,3,4 Daniel Öhlund,3,4 Abram Handly-Santana,4,8 Christine M. Ardito-Abraham,3,4 Michael Ludwig,3,4 Ela Elyada,3,4 Brinda Alagesan,3,4,9 Giulia Biffi,3,4 Georgi N. Yordanov,4,8 Bethany Delcuze,3,4 Brianna Creighton,3,4 Kevin Wright,3,4 Youngkyu Park,3,4 Folkert H.M. Morsink,10 I. Quintus Molenaar,11 Inne H. Borel Rinkes,11 Edwin Cuppen,1 Yuan Hao,3 Ying Jin,3 Isaac J. Nijman,1 Christine Iacobuzio-Donahue,6 Steven D. Leach,6 Darryl J. Pappin,3 Molly Hammell,3 David S. Klimstra,12 Olca Basturk,12 Ralph H. Hruban,13 George Johan Offerhaus,10 Robert G.J. Vries,1,2 Hans Clevers,1,* and David A. Tuveson3,4,6,*

1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584 CT Utrecht, the Netherlands
2foundation Hubrecht Organoid Technology (HUB), 3584 CT Utrecht, the Netherlands
3Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
4Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA
5Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY 11794, USA
6Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
7Weill Medical College at Cornell University, New York, NY 10065, USA
8Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
9Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA
10Department of Pathology, University Medical Centre Utrecht, 3584 CX Utrecht, the Netherlands
11Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands
12Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
13The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
14Co-first author
15Present address: Gurdon Institute-University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK

*Correspondence: Hans Clevers, David A. Tuveson

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.

논문정보
- 형식: Research article
- 게재일: 2014년 12월 (BRIC 등록일 2017-04-13)
- 연구진: 국외연구진
- 분야: Cell_Biology, Biochemistry, Molecular_Biology
- 피인용횟수: 최근 3년간 60회 이상 인용된 논문
광유전학의 과거, 현재와 미래[Neuron]
김윤석
발표: 김윤석 (Stanford University)
일자: 2020년 7월 30일 (목) 오후 02시 (한국시간)
언어: 한국어
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