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Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance

Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, whic...

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Autores principales: Al-Akkad, Walid, Acedo, Pilar, Vilia, Maria-Giovanna, Frenguelli, Luca, Ney, Alexander, Rodriguez-Hernandez, Irene, Labib, Peter L., Tamburrino, Domenico, Spoletini, Gabriele, Hall, Andrew R., Canestrari, Simone, Osnato, Anna, Garcia-Bernardo, Jose, Sejour, Leinal, Vassileva, Vessela, Vlachos, Ioannis S., Fusai, Giuseppe, Luong, Tu Vinh, Whittaker, Steven R., Pereira, Stephen P., Vallier, Ludovic, Pinzani, Massimo, Rombouts, Krista, Mazza, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688243/
https://www.ncbi.nlm.nih.gov/pubmed/36429078
http://dx.doi.org/10.3390/cells11223652
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author Al-Akkad, Walid
Acedo, Pilar
Vilia, Maria-Giovanna
Frenguelli, Luca
Ney, Alexander
Rodriguez-Hernandez, Irene
Labib, Peter L.
Tamburrino, Domenico
Spoletini, Gabriele
Hall, Andrew R.
Canestrari, Simone
Osnato, Anna
Garcia-Bernardo, Jose
Sejour, Leinal
Vassileva, Vessela
Vlachos, Ioannis S.
Fusai, Giuseppe
Luong, Tu Vinh
Whittaker, Steven R.
Pereira, Stephen P.
Vallier, Ludovic
Pinzani, Massimo
Rombouts, Krista
Mazza, Giuseppe
author_facet Al-Akkad, Walid
Acedo, Pilar
Vilia, Maria-Giovanna
Frenguelli, Luca
Ney, Alexander
Rodriguez-Hernandez, Irene
Labib, Peter L.
Tamburrino, Domenico
Spoletini, Gabriele
Hall, Andrew R.
Canestrari, Simone
Osnato, Anna
Garcia-Bernardo, Jose
Sejour, Leinal
Vassileva, Vessela
Vlachos, Ioannis S.
Fusai, Giuseppe
Luong, Tu Vinh
Whittaker, Steven R.
Pereira, Stephen P.
Vallier, Ludovic
Pinzani, Massimo
Rombouts, Krista
Mazza, Giuseppe
author_sort Al-Akkad, Walid
collection PubMed
description Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture.
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spelling pubmed-96882432022-11-25 Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance Al-Akkad, Walid Acedo, Pilar Vilia, Maria-Giovanna Frenguelli, Luca Ney, Alexander Rodriguez-Hernandez, Irene Labib, Peter L. Tamburrino, Domenico Spoletini, Gabriele Hall, Andrew R. Canestrari, Simone Osnato, Anna Garcia-Bernardo, Jose Sejour, Leinal Vassileva, Vessela Vlachos, Ioannis S. Fusai, Giuseppe Luong, Tu Vinh Whittaker, Steven R. Pereira, Stephen P. Vallier, Ludovic Pinzani, Massimo Rombouts, Krista Mazza, Giuseppe Cells Article Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture. MDPI 2022-11-17 /pmc/articles/PMC9688243/ /pubmed/36429078 http://dx.doi.org/10.3390/cells11223652 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Al-Akkad, Walid
Acedo, Pilar
Vilia, Maria-Giovanna
Frenguelli, Luca
Ney, Alexander
Rodriguez-Hernandez, Irene
Labib, Peter L.
Tamburrino, Domenico
Spoletini, Gabriele
Hall, Andrew R.
Canestrari, Simone
Osnato, Anna
Garcia-Bernardo, Jose
Sejour, Leinal
Vassileva, Vessela
Vlachos, Ioannis S.
Fusai, Giuseppe
Luong, Tu Vinh
Whittaker, Steven R.
Pereira, Stephen P.
Vallier, Ludovic
Pinzani, Massimo
Rombouts, Krista
Mazza, Giuseppe
Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance
title Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance
title_full Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance
title_fullStr Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance
title_full_unstemmed Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance
title_short Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance
title_sort tissue-specific human extracellular matrix scaffolds promote pancreatic tumour progression and chemotherapy resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688243/
https://www.ncbi.nlm.nih.gov/pubmed/36429078
http://dx.doi.org/10.3390/cells11223652
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