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Pathophysiological role of microRNA-29 in pancreatic cancer stroma
Dense fibrotic stroma associated with pancreatic ductal adenocarcinoma (PDAC) is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Current, anti-stromal therapies have failed to improve tumor response to chemotherapy and patient survival....
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476113/ https://www.ncbi.nlm.nih.gov/pubmed/26095125 http://dx.doi.org/10.1038/srep11450 |
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author | Kwon, Jason J. Nabinger, Sarah C. Vega, Zachary Sahu, Smiti Snigdha Alluri, Ravi K. Abdul-Sater, Zahi Yu, Zhangsheng Gore, Jesse Nalepa, Grzegorz Saxena, Romil Korc, Murray Kota, Janaiah |
author_facet | Kwon, Jason J. Nabinger, Sarah C. Vega, Zachary Sahu, Smiti Snigdha Alluri, Ravi K. Abdul-Sater, Zahi Yu, Zhangsheng Gore, Jesse Nalepa, Grzegorz Saxena, Romil Korc, Murray Kota, Janaiah |
author_sort | Kwon, Jason J. |
collection | PubMed |
description | Dense fibrotic stroma associated with pancreatic ductal adenocarcinoma (PDAC) is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Current, anti-stromal therapies have failed to improve tumor response to chemotherapy and patient survival. Furthermore, recent studies show that stroma impedes tumor progression, and its complete ablation accelerates PDAC progression. In an effort to understand the molecular mechanisms associated with tumor-stromal interactions, using in vitro and in vivo models and PDAC patient biopsies, we show that the loss of miR-29 is a common phenomenon of activated pancreatic stellate cells (PSCs)/fibroblasts, the major stromal cells responsible for fibrotic stromal reaction. Loss of miR-29 is correlated with a significant increase in extracellular matrix (ECM) deposition, a major component in PDAC stroma. Our in vitro miR-29 gain/loss-of-function studies document the role of miR-29 in PSC-mediated ECM stromal protein accumulation. Overexpression of miR-29 in activated stellate cells reduced stromal deposition, cancer cell viability, and cancer growth in co-culture. Furthermore, the loss of miR-29 in TGF-β1 activated PSCs is SMAD3 dependent. These results provide insights into the mechanistic role of miR-29 in PDAC stroma and its potential use as a therapeutic agent to target PDAC. |
format | Online Article Text |
id | pubmed-4476113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44761132015-06-24 Pathophysiological role of microRNA-29 in pancreatic cancer stroma Kwon, Jason J. Nabinger, Sarah C. Vega, Zachary Sahu, Smiti Snigdha Alluri, Ravi K. Abdul-Sater, Zahi Yu, Zhangsheng Gore, Jesse Nalepa, Grzegorz Saxena, Romil Korc, Murray Kota, Janaiah Sci Rep Article Dense fibrotic stroma associated with pancreatic ductal adenocarcinoma (PDAC) is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Current, anti-stromal therapies have failed to improve tumor response to chemotherapy and patient survival. Furthermore, recent studies show that stroma impedes tumor progression, and its complete ablation accelerates PDAC progression. In an effort to understand the molecular mechanisms associated with tumor-stromal interactions, using in vitro and in vivo models and PDAC patient biopsies, we show that the loss of miR-29 is a common phenomenon of activated pancreatic stellate cells (PSCs)/fibroblasts, the major stromal cells responsible for fibrotic stromal reaction. Loss of miR-29 is correlated with a significant increase in extracellular matrix (ECM) deposition, a major component in PDAC stroma. Our in vitro miR-29 gain/loss-of-function studies document the role of miR-29 in PSC-mediated ECM stromal protein accumulation. Overexpression of miR-29 in activated stellate cells reduced stromal deposition, cancer cell viability, and cancer growth in co-culture. Furthermore, the loss of miR-29 in TGF-β1 activated PSCs is SMAD3 dependent. These results provide insights into the mechanistic role of miR-29 in PDAC stroma and its potential use as a therapeutic agent to target PDAC. Nature Publishing Group 2015-06-22 /pmc/articles/PMC4476113/ /pubmed/26095125 http://dx.doi.org/10.1038/srep11450 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Kwon, Jason J. Nabinger, Sarah C. Vega, Zachary Sahu, Smiti Snigdha Alluri, Ravi K. Abdul-Sater, Zahi Yu, Zhangsheng Gore, Jesse Nalepa, Grzegorz Saxena, Romil Korc, Murray Kota, Janaiah Pathophysiological role of microRNA-29 in pancreatic cancer stroma |
title | Pathophysiological role of microRNA-29 in pancreatic cancer stroma |
title_full | Pathophysiological role of microRNA-29 in pancreatic cancer stroma |
title_fullStr | Pathophysiological role of microRNA-29 in pancreatic cancer stroma |
title_full_unstemmed | Pathophysiological role of microRNA-29 in pancreatic cancer stroma |
title_short | Pathophysiological role of microRNA-29 in pancreatic cancer stroma |
title_sort | pathophysiological role of microrna-29 in pancreatic cancer stroma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476113/ https://www.ncbi.nlm.nih.gov/pubmed/26095125 http://dx.doi.org/10.1038/srep11450 |
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