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Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer.

Cox TR, Erler JT - Dis Model Mech (2011)

Bottom Line: Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world.Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies.This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK Tumour Cell Signalling Unit, Section of Cell and Molecular Biology, The Institute of Cancer Research, London, UK.

ABSTRACT
Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

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Variations in tissue stiffness. The biomechanical properties of a tissue in terms of stiffness (elastic modulus), measured in pascals (Pa), vary markedly between organs and tissues, and are inherently related to tissue function. Mechanically static tissues such as brain or compliant tissues such as lung exhibit low stiffness, whereas tissues exposed to high mechanical loading, such as bone or skeletal muscle, exhibit elastic moduli with a stiffness that is several orders of magnitude greater. Tumorigenesis is typically associated with an increase in matrix and tissue stiffness, as in breast cancer. Adapted, with permission, from Butcher et al. (Butcher et al., 2009).
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f1-0040165: Variations in tissue stiffness. The biomechanical properties of a tissue in terms of stiffness (elastic modulus), measured in pascals (Pa), vary markedly between organs and tissues, and are inherently related to tissue function. Mechanically static tissues such as brain or compliant tissues such as lung exhibit low stiffness, whereas tissues exposed to high mechanical loading, such as bone or skeletal muscle, exhibit elastic moduli with a stiffness that is several orders of magnitude greater. Tumorigenesis is typically associated with an increase in matrix and tissue stiffness, as in breast cancer. Adapted, with permission, from Butcher et al. (Butcher et al., 2009).

Mentions: Functionally discrete tissues and organs have markedly distinct biomechanical properties (Fig. 1), which are subject to change during the course of development or during pathogenesis (Butcher et al., 2009). The biomechanical properties of the ECM are tightly controlled by the specific composition and concentration of matrix components, and also by post-translational modifications, such as glycosylation, transglutamination and cross-linking (Erler and Weaver, 2009).


Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer.

Cox TR, Erler JT - Dis Model Mech (2011)

Variations in tissue stiffness. The biomechanical properties of a tissue in terms of stiffness (elastic modulus), measured in pascals (Pa), vary markedly between organs and tissues, and are inherently related to tissue function. Mechanically static tissues such as brain or compliant tissues such as lung exhibit low stiffness, whereas tissues exposed to high mechanical loading, such as bone or skeletal muscle, exhibit elastic moduli with a stiffness that is several orders of magnitude greater. Tumorigenesis is typically associated with an increase in matrix and tissue stiffness, as in breast cancer. Adapted, with permission, from Butcher et al. (Butcher et al., 2009).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3046088&req=5

f1-0040165: Variations in tissue stiffness. The biomechanical properties of a tissue in terms of stiffness (elastic modulus), measured in pascals (Pa), vary markedly between organs and tissues, and are inherently related to tissue function. Mechanically static tissues such as brain or compliant tissues such as lung exhibit low stiffness, whereas tissues exposed to high mechanical loading, such as bone or skeletal muscle, exhibit elastic moduli with a stiffness that is several orders of magnitude greater. Tumorigenesis is typically associated with an increase in matrix and tissue stiffness, as in breast cancer. Adapted, with permission, from Butcher et al. (Butcher et al., 2009).
Mentions: Functionally discrete tissues and organs have markedly distinct biomechanical properties (Fig. 1), which are subject to change during the course of development or during pathogenesis (Butcher et al., 2009). The biomechanical properties of the ECM are tightly controlled by the specific composition and concentration of matrix components, and also by post-translational modifications, such as glycosylation, transglutamination and cross-linking (Erler and Weaver, 2009).

Bottom Line: Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world.Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies.This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK Tumour Cell Signalling Unit, Section of Cell and Molecular Biology, The Institute of Cancer Research, London, UK.

ABSTRACT
Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

Show MeSH
Related in: MedlinePlus