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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2018.00431/full |
| _version_ | 1818475664942039040 |
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| author | Valentina Poltavets Marina Kochetkova Stuart M. Pitson Stuart M. Pitson Michael S. Samuel Michael S. Samuel |
| author_facet | Valentina Poltavets Marina Kochetkova Stuart M. Pitson Stuart M. Pitson Michael S. Samuel Michael S. Samuel |
| author_sort | Valentina Poltavets |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T09:15:39Z |
| format | Article |
| id | doaj.art-89581314e0ee48328c07233917986b40 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T09:15:39Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-89581314e0ee48328c07233917986b402022-12-22T01:54:52ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2018-10-01810.3389/fonc.2018.00431378027The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell PlasticityValentina Poltavets0Marina Kochetkova1Stuart M. Pitson2Stuart M. Pitson3Michael S. Samuel4Michael S. Samuel5Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, AustraliaCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, AustraliaCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, AustraliaAdelaide Medical School, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, AustraliaCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, AustraliaAdelaide Medical School, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, AustraliaThe 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.https://www.frontiersin.org/article/10.3389/fonc.2018.00431/fullextracellular matrixstromaplasticitycancer associated fibroblasts (CAF)tumor associated macrophagestumor microenvironment |
| spellingShingle | Valentina Poltavets Marina Kochetkova Stuart M. Pitson Stuart M. Pitson Michael S. Samuel Michael S. Samuel The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity Frontiers in Oncology extracellular matrix stroma plasticity cancer associated fibroblasts (CAF) tumor associated macrophages tumor microenvironment |
| 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 | extracellular matrix stroma plasticity cancer associated fibroblasts (CAF) tumor associated macrophages tumor microenvironment |
| url | https://www.frontiersin.org/article/10.3389/fonc.2018.00431/full |
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