Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from...

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Main Authors:	Roy, David M, Walsh, Logan A
Format:	Online
Language:	English
Published:	Dove Medical Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090043/

id	pubmed-4090043
recordtype	oai_dc
spelling	pubmed-40900432014-08-11 Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors Roy, David M Walsh, Logan A Review The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease. Dove Medical Press 2014-07-03 /pmc/articles/PMC4090043/ /pubmed/25114586 http://dx.doi.org/10.2147/BCTT.S46020 Text en © 2014 Roy and Walsh. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Roy, David M Walsh, Logan A
spellingShingle	Roy, David M Walsh, Logan A Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
author_facet	Roy, David M Walsh, Logan A
author_sort	Roy, David M
title	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_short	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_full	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_fullStr	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_full_unstemmed	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_sort	candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
description	The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease.
publisher	Dove Medical Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090043/
_version_	1613110852062281728

Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

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