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Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades

Spatial and temporal regulation of the pericellular proteolytic environment by local growth factors, such as EGF and TGF-β, initiates a wide repertoire of cellular responses coupled to a plasmin/matrix metalloproteinase (MMP) dependent stromal-remodeling axis. Cell motility and invasion, tumor metas...

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Autores principales: Wilkins-Port, Cynthia E., Higgins, Stephen P., Higgins, Craig E., Kobori-Hotchkiss, Issey, Higgins, Paul J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290807/
https://www.ncbi.nlm.nih.gov/pubmed/22454771
http://dx.doi.org/10.1155/2012/454368
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author Wilkins-Port, Cynthia E.
Higgins, Stephen P.
Higgins, Craig E.
Kobori-Hotchkiss, Issey
Higgins, Paul J.
author_facet Wilkins-Port, Cynthia E.
Higgins, Stephen P.
Higgins, Craig E.
Kobori-Hotchkiss, Issey
Higgins, Paul J.
author_sort Wilkins-Port, Cynthia E.
collection PubMed
description Spatial and temporal regulation of the pericellular proteolytic environment by local growth factors, such as EGF and TGF-β, initiates a wide repertoire of cellular responses coupled to a plasmin/matrix metalloproteinase (MMP) dependent stromal-remodeling axis. Cell motility and invasion, tumor metastasis, wound healing, and organ fibrosis, for example, represent diverse events controlled by expression of a subset of genes that encode various classes of tissue remodeling proteins. These include members of the serine protease and MMP families that functionally constitute a complex system of interacting protease cascades and titrated by their respective inhibitors. Several structural components of the extracellular matrix are upregulated by TGF-β as are matrix-active proteases (e.g., urokinase (uPA), plasmin, MMP-1, -3, -9, -10, -11, -13, -14). Stringent controls on serine protease/MMP expression and their topographic activity are essential for maintaining tissue homeostasis. Targeting individual elements in this highly interactive network may lead to novel therapeutic approaches for the treatment of cancer, fibrotic diseases, and chronic wounds.
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spelling pubmed-32908072012-03-27 Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades Wilkins-Port, Cynthia E. Higgins, Stephen P. Higgins, Craig E. Kobori-Hotchkiss, Issey Higgins, Paul J. Biochem Res Int Review Article Spatial and temporal regulation of the pericellular proteolytic environment by local growth factors, such as EGF and TGF-β, initiates a wide repertoire of cellular responses coupled to a plasmin/matrix metalloproteinase (MMP) dependent stromal-remodeling axis. Cell motility and invasion, tumor metastasis, wound healing, and organ fibrosis, for example, represent diverse events controlled by expression of a subset of genes that encode various classes of tissue remodeling proteins. These include members of the serine protease and MMP families that functionally constitute a complex system of interacting protease cascades and titrated by their respective inhibitors. Several structural components of the extracellular matrix are upregulated by TGF-β as are matrix-active proteases (e.g., urokinase (uPA), plasmin, MMP-1, -3, -9, -10, -11, -13, -14). Stringent controls on serine protease/MMP expression and their topographic activity are essential for maintaining tissue homeostasis. Targeting individual elements in this highly interactive network may lead to novel therapeutic approaches for the treatment of cancer, fibrotic diseases, and chronic wounds. Hindawi Publishing Corporation 2012 2012-02-20 /pmc/articles/PMC3290807/ /pubmed/22454771 http://dx.doi.org/10.1155/2012/454368 Text en Copyright © 2012 Cynthia E. Wilkins-Port et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Wilkins-Port, Cynthia E.
Higgins, Stephen P.
Higgins, Craig E.
Kobori-Hotchkiss, Issey
Higgins, Paul J.
Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades
title Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades
title_full Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades
title_fullStr Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades
title_full_unstemmed Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades
title_short Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades
title_sort complex regulation of the pericellular proteolytic microenvironment during tumor progression and wound repair: functional interactions between the serine protease and matrix metalloproteinase cascades
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290807/
https://www.ncbi.nlm.nih.gov/pubmed/22454771
http://dx.doi.org/10.1155/2012/454368
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