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The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity
The microenvironment encompasses all components of a tumor other than the cancer cells themselves. It is highly heterogenous, comprising a cellular component that includes immune cells, fibroblasts, adipocytes, and endothelial cells, and a non-cellular component, which is a meshwork of polymeric pro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189298/ https://www.ncbi.nlm.nih.gov/pubmed/30356678 http://dx.doi.org/10.3389/fonc.2018.00431 |
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author | Poltavets, Valentina Kochetkova, Marina Pitson, Stuart M. Samuel, Michael S. |
author_facet | Poltavets, Valentina Kochetkova, Marina Pitson, Stuart M. Samuel, Michael S. |
author_sort | Poltavets, Valentina |
collection | PubMed |
description | The microenvironment encompasses all components of a tumor other than the cancer cells themselves. It is highly heterogenous, comprising a cellular component that includes immune cells, fibroblasts, adipocytes, and endothelial cells, and a non-cellular component, which is a meshwork of polymeric proteins and accessory molecules, termed the extracellular matrix (ECM). The ECM provides both a biochemical and biomechanical context within which cancer cells exist. Cancer progression is dependent on the ability of cancer cells to traverse the ECM barrier, access the circulation and establish distal metastases. Communication between cancer cells and the microenvironment is therefore an important aspect of tumor progression. Significant progress has been made in identifying the molecular mechanisms that enable cancer cells to subvert the immune component of the microenvironment to facilitate tumor growth and spread. While much less is known about how the tumor cells adapt to changes in the ECM nor indeed how they influence ECM structure and composition, the importance of the ECM to cancer progression is now well established. Plasticity refers to the ability of cancer cells to modify their physiological characteristics, permitting them to survive hostile microenvironments and resist therapy. Examples include the acquisition of stemness characteristics and the epithelial-mesenchymal and mesenchymal-epithelial transitions. There is emerging evidence that the biochemical and biomechanical properties of the ECM influence cancer cell plasticity and vice versa. Outstanding challenges for the field remain the identification of the cellular mechanisms by which cancer cells establish tumor-promoting ECM characteristics and delineating the key molecular mechanisms underlying ECM-induced cancer cell plasticity. Here we summarize the current state of understanding about the relationships between cancer cells and the main stromal cell types of the microenvironment that determine ECM characteristics, and the key molecular pathways that govern this three-way interaction to regulate cancer cell plasticity. We postulate that a comprehensive understanding of this dynamic system will be required to fully exploit opportunities for targeting the ECM regulators of cancer cell plasticity. |
format | Online Article Text |
id | pubmed-6189298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61892982018-10-23 The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity Poltavets, Valentina Kochetkova, Marina Pitson, Stuart M. Samuel, Michael S. Front Oncol Oncology The microenvironment encompasses all components of a tumor other than the cancer cells themselves. It is highly heterogenous, comprising a cellular component that includes immune cells, fibroblasts, adipocytes, and endothelial cells, and a non-cellular component, which is a meshwork of polymeric proteins and accessory molecules, termed the extracellular matrix (ECM). The ECM provides both a biochemical and biomechanical context within which cancer cells exist. Cancer progression is dependent on the ability of cancer cells to traverse the ECM barrier, access the circulation and establish distal metastases. Communication between cancer cells and the microenvironment is therefore an important aspect of tumor progression. Significant progress has been made in identifying the molecular mechanisms that enable cancer cells to subvert the immune component of the microenvironment to facilitate tumor growth and spread. While much less is known about how the tumor cells adapt to changes in the ECM nor indeed how they influence ECM structure and composition, the importance of the ECM to cancer progression is now well established. Plasticity refers to the ability of cancer cells to modify their physiological characteristics, permitting them to survive hostile microenvironments and resist therapy. Examples include the acquisition of stemness characteristics and the epithelial-mesenchymal and mesenchymal-epithelial transitions. There is emerging evidence that the biochemical and biomechanical properties of the ECM influence cancer cell plasticity and vice versa. Outstanding challenges for the field remain the identification of the cellular mechanisms by which cancer cells establish tumor-promoting ECM characteristics and delineating the key molecular mechanisms underlying ECM-induced cancer cell plasticity. Here we summarize the current state of understanding about the relationships between cancer cells and the main stromal cell types of the microenvironment that determine ECM characteristics, and the key molecular pathways that govern this three-way interaction to regulate cancer cell plasticity. We postulate that a comprehensive understanding of this dynamic system will be required to fully exploit opportunities for targeting the ECM regulators of cancer cell plasticity. Frontiers Media S.A. 2018-10-09 /pmc/articles/PMC6189298/ /pubmed/30356678 http://dx.doi.org/10.3389/fonc.2018.00431 Text en Copyright © 2018 Poltavets, Kochetkova, Pitson and Samuel. http://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 Poltavets, Valentina Kochetkova, Marina Pitson, Stuart M. Samuel, Michael S. The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity |
title | The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity |
title_full | The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity |
title_fullStr | The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity |
title_full_unstemmed | The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity |
title_short | The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity |
title_sort | role of the extracellular matrix and its molecular and cellular regulators in cancer cell plasticity |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189298/ https://www.ncbi.nlm.nih.gov/pubmed/30356678 http://dx.doi.org/10.3389/fonc.2018.00431 |
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