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Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression
The cell of origin of pancreatic ductal adenocarcinoma (PDAC) has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668631/ https://www.ncbi.nlm.nih.gov/pubmed/29069604 http://dx.doi.org/10.1016/j.celrep.2017.09.093 |
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author | Ferreira, Rute M.M. Sancho, Rocio Messal, Hendrik A. Nye, Emma Spencer-Dene, Bradley Stone, Richard K. Stamp, Gordon Rosewell, Ian Quaglia, Alberto Behrens, Axel |
author_facet | Ferreira, Rute M.M. Sancho, Rocio Messal, Hendrik A. Nye, Emma Spencer-Dene, Bradley Stone, Richard K. Stamp, Gordon Rosewell, Ian Quaglia, Alberto Behrens, Axel |
author_sort | Ferreira, Rute M.M. |
collection | PubMed |
description | The cell of origin of pancreatic ductal adenocarcinoma (PDAC) has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs), duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development. |
format | Online Article Text |
id | pubmed-5668631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-56686312017-11-09 Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression Ferreira, Rute M.M. Sancho, Rocio Messal, Hendrik A. Nye, Emma Spencer-Dene, Bradley Stone, Richard K. Stamp, Gordon Rosewell, Ian Quaglia, Alberto Behrens, Axel Cell Rep Article The cell of origin of pancreatic ductal adenocarcinoma (PDAC) has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs), duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development. Cell Press 2017-10-24 /pmc/articles/PMC5668631/ /pubmed/29069604 http://dx.doi.org/10.1016/j.celrep.2017.09.093 Text en © 2017 Francis Crick Institute http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ferreira, Rute M.M. Sancho, Rocio Messal, Hendrik A. Nye, Emma Spencer-Dene, Bradley Stone, Richard K. Stamp, Gordon Rosewell, Ian Quaglia, Alberto Behrens, Axel Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression |
title | Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression |
title_full | Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression |
title_fullStr | Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression |
title_full_unstemmed | Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression |
title_short | Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression |
title_sort | duct- and acinar-derived pancreatic ductal adenocarcinomas show distinct tumor progression and marker expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668631/ https://www.ncbi.nlm.nih.gov/pubmed/29069604 http://dx.doi.org/10.1016/j.celrep.2017.09.093 |
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