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The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies

Pancreatic ductal adenocarcinoma (PDAC) is notorious for a dense fibrotic stroma that is interlaced with a collagen-based extracellular matrix (ECM) that plays an important role in tumor biology. Traditionally thought to only provide a physical barrier from host responses and systemic chemotherapy,...

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Autores principales: Perez, Vincent M., Kearney, Joseph F., Yeh, Jen Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526858/
https://www.ncbi.nlm.nih.gov/pubmed/34692532
http://dx.doi.org/10.3389/fonc.2021.751311
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author Perez, Vincent M.
Kearney, Joseph F.
Yeh, Jen Jen
author_facet Perez, Vincent M.
Kearney, Joseph F.
Yeh, Jen Jen
author_sort Perez, Vincent M.
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is notorious for a dense fibrotic stroma that is interlaced with a collagen-based extracellular matrix (ECM) that plays an important role in tumor biology. Traditionally thought to only provide a physical barrier from host responses and systemic chemotherapy, new studies have demonstrated that the ECM maintains biomechanical and biochemical properties of the tumor microenvironment (TME) and restrains tumor growth. Recent studies have shown that the ECM augments tumor stiffness, interstitial fluid pressure, cell-to-cell junctions, and microvascularity using a mix of biomechanical and biochemical signals to influence tumor fate for better or worse. In addition, PDAC tumors have been shown to use ECM-derived peptide fragments as a nutrient source in nutrient-poor conditions. While collagens are the most abundant proteins found in the ECM, several studies have identified growth factors, integrins, glycoproteins, and proteoglycans in the ECM. This review focuses on the dichotomous nature of the PDAC ECM, the types of collagens and other proteins found in the ECM, and therapeutic strategies targeting the PDAC ECM.
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spelling pubmed-85268582021-10-21 The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies Perez, Vincent M. Kearney, Joseph F. Yeh, Jen Jen Front Oncol Oncology Pancreatic ductal adenocarcinoma (PDAC) is notorious for a dense fibrotic stroma that is interlaced with a collagen-based extracellular matrix (ECM) that plays an important role in tumor biology. Traditionally thought to only provide a physical barrier from host responses and systemic chemotherapy, new studies have demonstrated that the ECM maintains biomechanical and biochemical properties of the tumor microenvironment (TME) and restrains tumor growth. Recent studies have shown that the ECM augments tumor stiffness, interstitial fluid pressure, cell-to-cell junctions, and microvascularity using a mix of biomechanical and biochemical signals to influence tumor fate for better or worse. In addition, PDAC tumors have been shown to use ECM-derived peptide fragments as a nutrient source in nutrient-poor conditions. While collagens are the most abundant proteins found in the ECM, several studies have identified growth factors, integrins, glycoproteins, and proteoglycans in the ECM. This review focuses on the dichotomous nature of the PDAC ECM, the types of collagens and other proteins found in the ECM, and therapeutic strategies targeting the PDAC ECM. Frontiers Media S.A. 2021-10-06 /pmc/articles/PMC8526858/ /pubmed/34692532 http://dx.doi.org/10.3389/fonc.2021.751311 Text en Copyright © 2021 Perez, Kearney and Yeh https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Perez, Vincent M.
Kearney, Joseph F.
Yeh, Jen Jen
The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies
title The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies
title_full The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies
title_fullStr The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies
title_full_unstemmed The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies
title_short The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies
title_sort pdac extracellular matrix: a review of the ecm protein composition, tumor cell interaction, and therapeutic strategies
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526858/
https://www.ncbi.nlm.nih.gov/pubmed/34692532
http://dx.doi.org/10.3389/fonc.2021.751311
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