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-Santana; Christine 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

doi:10.1016/j.cell.2014.12.021

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1574 Scopus citations

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.

Original language	English
Pages (from-to)	324-338
Number of pages	15
Journal	Cell
Volume	160
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cell.2014.12.021
State	Published - 15 Jan 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cell.2014.12.021

Cite this

Boj, S. F., Hwang, C. I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M. S., Gracanin, A., Oni, T., Yu, K. H., Van Boxtel, R., Huch, M., Rivera, K. D., Wilson, J. P., Feigin, M. E., Öhlund, D., ... Tuveson, D. A. (2015). Organoid models of human and mouse ductal pancreatic cancer. Cell, 160(1-2), 324-338. https://doi.org/10.1016/j.cell.2014.12.021

@article{de4ade086c7047bd8c2a538ce2235bf9,

title = "Organoid models of human and mouse ductal pancreatic cancer",

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.",

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

year = "2015",

month = jan,

day = "15",

doi = "10.1016/j.cell.2014.12.021",

language = "אנגלית",

volume = "160",

pages = "324--338",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "1-2",

}

Boj, SF, Hwang, CI, Baker, LA, Chio, IIC, Engle, DD, Corbo, V, Jager, M, Ponz-Sarvise, M, Tiriac, H, Spector, MS, Gracanin, A, Oni, T, Yu, KH, Van Boxtel, R, Huch, M, Rivera, KD, Wilson, JP, Feigin, ME, Öhlund, D, Handly-Santana, A, Ardito-Abraham, CM, Ludwig, M, Elyada, E, Alagesan, B, Biffi, G, Yordanov, GN, Delcuze, B, Creighton, B, Wright, K, Park, Y, Morsink, FHM, Molenaar, IQ, Borel Rinkes, IH, Cuppen, E, Hao, Y, Jin, Y, Nijman, IJ, Iacobuzio-Donahue, C, Leach, SD, Pappin, DJ, Hammell, M, Klimstra, DS, Basturk, O, Hruban, RH, Offerhaus, GJ, Vries, RGJ, Clevers, H & Tuveson, DA 2015, 'Organoid models of human and mouse ductal pancreatic cancer', Cell, vol. 160, no. 1-2, pp. 324-338. https://doi.org/10.1016/j.cell.2014.12.021

TY - JOUR

T1 - Organoid models of human and mouse ductal pancreatic cancer

AU - Boj, Sylvia F.

AU - Hwang, Chang Il

AU - Baker, Lindsey A.

AU - Chio, Iok In Christine

AU - Engle, Dannielle D.

AU - Corbo, Vincenzo

AU - Jager, Myrthe

AU - Ponz-Sarvise, Mariano

AU - Tiriac, Hervé

AU - Spector, Mona S.

AU - Gracanin, Ana

AU - Oni, Tobiloba

AU - Yu, Kenneth H.

AU - Van Boxtel, Ruben

AU - Huch, Meritxell

AU - Rivera, Keith D.

AU - Wilson, John P.

AU - Feigin, Michael E.

AU - Öhlund, Daniel

AU - Handly-Santana, Abram

AU - Ardito-Abraham, Christine M.

AU - Ludwig, Michael

AU - Elyada, Ela

AU - Alagesan, Brinda

AU - Biffi, Giulia

AU - Yordanov, Georgi N.

AU - Delcuze, Bethany

AU - Creighton, Brianna

AU - Wright, Kevin

AU - Park, Youngkyu

AU - Morsink, Folkert H.M.

AU - Molenaar, I. Quintus

AU - Borel Rinkes, Inne H.

AU - Cuppen, Edwin

AU - Hao, Yuan

AU - Jin, Ying

AU - Nijman, Isaac J.

AU - Iacobuzio-Donahue, Christine

AU - Leach, Steven D.

AU - Pappin, Darryl J.

AU - Hammell, Molly

AU - Klimstra, David S.

AU - Basturk, Olca

AU - Hruban, Ralph H.

AU - Offerhaus, George Johan

AU - Vries, Robert G.J.

AU - Clevers, Hans

AU - Tuveson, David A.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84920983131&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2014.12.021

DO - 10.1016/j.cell.2014.12.021

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 25557080

AN - SCOPUS:84920983131

SN - 0092-8674

VL - 160

SP - 324

EP - 338

JO - Cell

JF - Cell

IS - 1-2

ER -

Organoid models of human and mouse ductal pancreatic cancer

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this