MaltSci 麦伴科研

Appearance

Curated Papers > High-impact authoritative literature on "organoids"

Organoid models of human and mouse ductal pancreatic cancer. ​

Literature Information ​

PMID25557080
JournalCell
Impact Factor42.5
JCR QuartileQ1
Publication Year2015
Times Cited1183
KeywordsPancreatic cancer, Organoid models, Tumorigenesis
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
ISSN0092-8674
Pages324-38
Issue160(1-2)
AuthorsSylvia 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

TL;DR ​

This study establishes organoid models from both normal and neoplastic pancreatic tissues, highlighting their ability to mimic tumor progression and enabling genetic manipulation to explore pathways involved in pancreatic cancer. The findings underscore the potential of these organoids as a valuable platform for understanding the molecular characteristics of this lethal disease and advancing research into its diagnosis and treatment.

Search for more papers on MaltSci.com ​

Pancreatic cancer · Organoid models · Tumorigenesis

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.

MaltSci.com AI Research Service ​

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed ​

  1. What specific genetic manipulations have been most effective in studying pancreatic cancer using organoid models?
  2. How do the characteristics of murine pancreatic organoids compare to those derived from human tissues in terms of disease progression?
  3. What are the limitations of using organoid models for understanding the metastatic behavior of pancreatic cancer?
  4. How can organoid models contribute to the development of targeted therapies for pancreatic cancer?
  5. What role do transcriptional and proteomic analyses play in identifying potential biomarkers for pancreatic cancer in organoid studies?

Key Findings ​

Research Background and Purpose ​

Pancreatic cancer is one of the deadliest cancers, primarily due to its late-stage diagnosis and poor treatment responses. The need for effective methods to identify and study the pathways involved in pancreatic tumorigenesis is critical. This study aims to establish organoid models from both normal and neoplastic pancreatic tissues to facilitate research in pancreatic cancer.

Main Methods/Materials/Experimental Design ​

The study utilized organoid models derived from murine and human pancreatic tissues. The methodology can be summarized as follows:

Mermaid diagram
  1. Tissue Collection: Both normal and neoplastic pancreatic tissues were collected from resected tumors and biopsies.
  2. Organoid Culture: These tissues were cultured to establish organoid models that maintain specific characteristics of the original tissues.
  3. Characterization of Organoids: The organoids were characterized for their ductal and disease-stage-specific traits.
  4. Transplantation of Neoplastic Organoids: Neoplastic organoids were orthotopically transplanted into host mice to study tumor progression.
  5. Analysis of Tumor Development: The transplanted organoids were monitored for tumor development, including the progression from early neoplasms to invasive carcinomas.
  6. Transcriptional and Proteomic Analysis: Comprehensive analyses were conducted to identify gene and protein changes associated with disease progression.
  7. Comparison with Human Tissues: The findings from murine organoids were validated against human pancreatic cancer tissues.

Key Results and Findings ​

  • Organoid Viability: The organoids demonstrated the ability to survive cryopreservation and retain key characteristics of the original pancreatic tissues.
  • Tumor Recapitulation: Orthotopically transplanted neoplastic organoids successfully recapitulated the full spectrum of pancreatic tumor development, from early-stage neoplasms to metastatic carcinomas.
  • Molecular Insights: Transcriptional and proteomic analyses identified specific genes and pathways that are altered during pancreatic cancer progression. Many of these changes were confirmed in human tissues, indicating the relevance of the organoid model.

Main Conclusions/Significance/Innovation ​

The study establishes pancreatic organoids as a robust and versatile model system for investigating pancreatic cancer. Their ability to mimic the disease's progression and respond to genetic manipulations provides a powerful platform for exploring the molecular underpinnings of pancreatic tumorigenesis. This research highlights the potential of organoids in identifying new therapeutic targets and understanding the biology of this aggressive cancer.

Research Limitations and Future Directions ​

  • Limitations: The study primarily focuses on murine models, which may not fully replicate human disease complexity. The long-term effects of genetic manipulations on organoid behavior require further investigation.
  • Future Directions: Future research should aim to enhance the organoid models by incorporating a broader range of genetic backgrounds and exploring their response to various therapeutic agents. Additionally, longitudinal studies could provide deeper insights into tumor evolution and metastasis in pancreatic cancer.

References ​

  1. Protein labeling by iTRAQ: a new tool for quantitative mass spectrometry in proteome research. - Sebastian Wiese;Kai A Reidegeld;Helmut E Meyer;Bettina Warscheid - Proteomics (2007)
  2. An in vivo platform for translational drug development in pancreatic cancer. - Belen Rubio-Viqueira;Antonio Jimeno;George Cusatis;Xianfeng Zhang;Christine Iacobuzio-Donahue;Collins Karikari;Chanjusn Shi;Kathleen Danenberg;Peter V Danenberg;Hidekazu Kuramochi;Koji Tanaka;Sharat Singh;Hossein Salimi-Moosavi;Nadia Bouraoud;Maria L Amador;Soner Altiok;Piotr Kulesza;Charles Yeo;Wells Messersmith;James Eshleman;Ralph H Hruban;Anirban Maitra;Manuel Hidalgo - Clinical cancer research : an official journal of the American Association for Cancer Research (2006)
  3. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. - Sharon Y Gidekel Friedlander;Gerald C Chu;Eric L Snyder;Nomeda Girnius;Gregory Dibelius;Denise Crowley;Eliza Vasile;Ronald A DePinho;Tyler Jacks - Cancer cell (2009)
  4. Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. - Meritxell Rovira;Sherri-Gae Scott;Andrew S Liss;Jan Jensen;Sarah P Thayer;Steven D Leach - Proceedings of the National Academy of Sciences of the United States of America (2010)
  5. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. - Nick Barker;Meritxell Huch;Pekka Kujala;Marc van de Wetering;Hugo J Snippert;Johan H van Es;Toshiro Sato;Daniel E Stange;Harry Begthel;Maaike van den Born;Esther Danenberg;Stieneke van den Brink;Jeroen Korving;Arie Abo;Peter J Peters;Nick Wright;Richard Poulsom;Hans Clevers - Cell stem cell (2010)
  6. Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. - John P Morris;David A Cano;Shigeki Sekine;Sam C Wang;Matthias Hebrok - The Journal of clinical investigation (2010)
  7. Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents. - Sreenath V Sharma;Daniel A Haber;Jeff Settleman - Nature reviews. Cancer (2010)
  8. Gene regulation by nucleoporins and links to cancer. - Alwin Köhler;Ed Hurt - Molecular cell (2010)
  9. Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. - Maria C Villarroel;N V Rajeshkumar;Ignacio Garrido-Laguna;Ana De Jesus-Acosta;Siân Jones;Anirban Maitra;Ralph H Hruban;James R Eshleman;Alison Klein;Daniel Laheru;Ross Donehower;Manuel Hidalgo - Molecular cancer therapeutics (2011)
  10. Epithelial tissues have varying degrees of susceptibility to Kras(G12D)-initiated tumorigenesis in a mouse model. - Kevin C Ray;Kayla M Bell;Jingbo Yan;Guoqiang Gu;Christine H Chung;M Kay Washington;Anna L Means - PloS one (2011)

Literatures Citing This Work ​

  1. Pancreatic cancer: From normal to metastases--a whole gamut of pancreatic organoids. - Gillian Patman - Nature reviews. Gastroenterology & hepatology (2015)
  2. Toward recreating colon cancer in human organoids. - Ameen A Salahudeen;Calvin J Kuo - Nature medicine (2015)
  3. Organoid development in cancer genome discovery. - Dong Gao;Yu Chen - Current opinion in genetics & development (2015)
  4. Imaging tumor metabolism using positron emission tomography. - David Y Lewis;Dmitry Soloviev;Kevin M Brindle - Cancer journal (Sudbury, Mass.) (2015)
  5. Organoid modeling for cancer precision medicine. - Michael A Cantrell;Calvin J Kuo - Genome medicine (2015)
  6. Examining the utility of patient-derived xenograft mouse models. - Samuel Aparicio;Manuel Hidalgo;Andrew L Kung - Nature reviews. Cancer (2015)
  7. Translational value of mouse models in oncology drug development. - Stephen E Gould;Melissa R Junttila;Frederic J de Sauvage - Nature medicine (2015)
  8. Advances and applications of single-cell sequencing technologies. - Yong Wang;Nicholas E Navin - Molecular cell (2015)
  9. MYC in pancreatic cancer: novel mechanistic insights and their translation into therapeutic strategies. - E Hessmann;G Schneider;V Ellenrieder;J T Siveke - Oncogene (2016)
  10. The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma. - Nathan M Krah;Jean-Paul De La O;Galvin H Swift;Chinh Q Hoang;Spencer G Willet;Fong Chen Pan;Gabriela M Cash;Mary P Bronner;Christopher Ve Wright;Raymond J MacDonald;L Charles Murtaugh - eLife (2015)

... (1173 more literatures)

© 2025 MaltSci - We reshape scientific research with AI technology