Organoid Models of Human and Mouse Ductal Pancreatic Cancer

被引：1583

作者：

Boj, Sylvia F. ^{[1
,2
,3
]}

Hwang, Chang-Il ^{[4
,5
]}

Baker, Lindsey A. ^{[4
,5
]}

Chio, Iok In Christine ^{[4
,5
]}

Engle, Dannielle D. ^{[4
,5
]}

Corbo, Vincenzo ^{[4
,5
]}

Jager, Myrthe ^{[1
,2
]}

Ponz-Sarvise, Mariano ^{[4
,5
]}

Tiriac, Herve ^{[4
,5
]}

Spector, Mona S. ^{[4
,5
]}

Gracanin, Ana ^{[1
,2
,3
]}

Oni, Tobiloba ^{[4
,5
,6
]}

Yu, Kenneth H. ^{[4
,5
,7
,8
]}

van Boxtel, Ruben ^{[1
,2
]}

Huch, Meritxell ^{[1
,2
]}

Rivera, Keith D. ^{[4
]}

Wilson, John P. ^{[4
]}

Feigin, Michael E. ^{[4
,5
]}

Oehlund, Daniel ^{[4
,5
]}

Handly-Santana, Abram ^{[5
,9
]}

Ardito-Abraham, Christine M. ^{[4
,5
]}

Ludwig, Michael ^{[4
,5
]}

Elyada, Ela ^{[4
,5
]}

Alagesan, Brinda ^{[4
,5
,10
]}

Biffi, Giulia ^{[4
,5
]}

Yordanov, Georgi N. ^{[5
,9
]}

Delcuze, Bethany ^{[4
,5
]}

Creighton, Brianna ^{[4
,5
]}

Wright, Kevin ^{[4
,5
]}

Park, Youngkyu ^{[4
,5
]}

Morsink, Folkert H. M. ^{[11
]}

Molenaar, I. Quintus ^{[12
]}

Rinkes, Inne H. Borel ^{[12
]}

Cuppen, Edwin ^{[1
,2
]}

Hao, Yuan ^{[4
]}

Jin, Ying ^{[4
]}

Nijman, Isaac J. ^{[1
,2
]}

Iacobuzio-Donahue, Christine ^{[7
]}

Leach, Steven D. ^{[7
]}

Pappin, Darryl J. ^{[4
]}

Hammell, Molly ^{[4
]}

Klimstra, David S. ^{[13
]}

Basturk, Olca ^{[13
]}

Hruban, Ralph H. ^{[14
]}

Offerhaus, George Johan ^{[11
]}

Vries, Robert G. J. ^{[1
,2
,3
]}

Clevers, Hans ^{[1
,2
]}

Tuveson, David A. ^{[4
,5
,7
]}

机构：

[1] Univ Med Ctr Utrecht, Hubrecht Inst, Royal Netherlands Acad Arts & Sci KNAW, NL-3584 CT Utrecht, Netherlands

[2] CancerGenom Nl, NL-3584 CT Utrecht, Netherlands

[3] Fdn Hubrecht Organoid Technol HUB, NL-3584 CT Utrecht, Netherlands

[4] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[5] Lustgarten Fdn Pancreat Canc Res Lab, Cold Spring Harbor, NY 11724 USA

[6] SUNY Stony Brook, Grad Program Mol & Cellular Biol, Stony Brook, NY 11794 USA

[7] Mem Sloan Kettering Canc Ctr, Rubenstein Ctr Pancreat Canc Res, New York, NY 10065 USA

[8] Cornell Univ, Weill Med Coll, New York, NY 10065 USA

[9] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA

[10] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA

[11] Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CX Utrecht, Netherlands

[12] Univ Med Ctr Utrecht, Dept Surg, NL-3584 CX Utrecht, Netherlands

[13] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[14] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA

来源：

CELL | 2015年 / 160卷 / 1-2期

基金：

瑞典研究理事会;

关键词：

ACINAR-CELL TRANSDIFFERENTIATION; IN-VITRO EXPANSION; ONCOGENIC KRAS; EXPRESSION PROFILES; PROGENITOR CELLS; ADENOCARCINOMA; MICE; NEOPLASIA; PROMOTES; IDENTIFICATION;

D O I：

10.1016/j.cell.2014.12.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：324 / 338

页数：15

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