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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)324-338
Number of pages15
JournalCell
Volume160
Issue number1-2
DOIs
StatePublished - Jan 15 2015

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Organoids
Pancreatic Neoplasms
Tumors
Tissue
Biopsy
Genes
Neoplasms
Proteins
Delayed Diagnosis
Cryopreservation
Proteomics
Disease Progression
Pancreas
Carcinogenesis
Carcinoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Boj, S. F., Hwang, C. I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., ... 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

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

In: Cell, Vol. 160, No. 1-2, 15.01.2015, p. 324-338.

Research output: Contribution to journalArticle

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
Boj SF, Hwang CI, Baker LA, Chio IIC, Engle DD, Corbo V et al. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015 Jan 15;160(1-2):324-338. https://doi.org/10.1016/j.cell.2014.12.021
Boj, Sylvia F. ; Hwang, Chang Il ; Baker, Lindsey A. ; Chio, Iok In Christine ; Engle, Dannielle D. ; Corbo, Vincenzo ; Jager, Myrthe ; Ponz-Sarvise, Mariano ; Tiriac, Hervé ; Spector, Mona S. ; Gracanin, Ana ; Oni, Tobiloba ; Yu, Kenneth H. ; Van Boxtel, Ruben ; Huch, Meritxell ; Rivera, Keith D. ; Wilson, John P. ; Feigin, Michael E. ; Öhlund, Daniel ; Handly-Santana, Abram ; Ardito-Abraham, Christine M. ; Ludwig, Michael ; Elyada, Ela ; Alagesan, Brinda ; Biffi, Giulia ; Yordanov, Georgi N. ; Delcuze, Bethany ; Creighton, Brianna ; Wright, Kevin ; Park, Youngkyu ; Morsink, Folkert H M ; Molenaar, I. Quintus ; Borel Rinkes, Inne H. ; Cuppen, Edwin ; Hao, Yuan ; Jin, Ying ; Nijman, Isaac J. ; Iacobuzio-Donahue, Christine ; Leach, Steven D. ; Pappin, Darryl J. ; Hammell, Molly ; Klimstra, David S. ; Basturk, Olca ; Hruban, Ralph H ; Offerhaus, George Johan ; Vries, Robert G J ; Clevers, Hans ; Tuveson, David A. / Organoid models of human and mouse ductal pancreatic cancer. In: Cell. 2015 ; Vol. 160, No. 1-2. pp. 324-338.
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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.",
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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.

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