Special Issue "Matrix Metalloproteinases in Cancer Progress"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 December 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Constance E. Brinckerhoff

Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Rubin 602, 1 Medical Center Drive, Lebanon, NH 03756, USA
Website | E-Mail
Fax: +1-603-653-9952
Interests: melanoma, breast cancer, lung cancer, signal transduction, protease activated receptor-1 (par-1); angiogenesis, mmp-1, transcription, gene expression

Special Issue Information

Dear Colleagues,

The importance of MMPs in connective tissue remodeling and matrix degradation have been known for a long time. Increasingly, it is recognized that these enzymes have critical roles in signal transduction and gene regulation, and that they may have beneficial functions in normal homeostasis as well as in diseases. This special issue is dedicated to highlighting the more novel and innovative roles of secreted MMPs and their membrane bound counterparts, MT-MMPs, as mediators of cancer progression and as tumor suppressors. In addition, these enzymes may participate in cancers by functioning in organelles, such as exosomes and invadopodia. Thus, with their ubiquitous presence, they continue to represent attractive therapeutic targets and new strategies with improved efficacy are emerging. Finally, innovative models of cancers, such as zebrafish, may provide critical insights into how MMPs contribute to cancer progression.

Prof. Dr. Constance E. Brinckerhoff
Guest Editor

Submission

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Keywords

  • novel roles of MMPs in tumor progression and suppression
  • gene regulation
  • signal transduction
  • model systems
  • organelles
  • therapeutic strategies

Published Papers (9 papers)

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Review

Open AccessReview Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer
Cancers 2015, 7(1), 329-341; doi:10.3390/cancers7010329
Received: 27 November 2014 / Revised: 22 December 2014 / Accepted: 29 January 2015 / Published: 5 February 2015
Cited by 2 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text
Abstract
Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung
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Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Open AccessReview Fibrogenesis and Carcinogenesis in Nonalcoholic Steatohepatitis (NASH): Involvement of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinase (TIMPs)
Cancers 2014, 6(3), 1220-1255; doi:10.3390/cancers6031220
Received: 7 March 2014 / Revised: 24 April 2014 / Accepted: 15 May 2014 / Published: 27 June 2014
Cited by 9 | PDF Full-text (1505 KB) | HTML Full-text | XML Full-text
Abstract
Nonalcoholic steatohepatitis (NASH) is emerging worldwide because life-styles have changed to include much over-eating and less physical activity. The clinical and pathophysiological features of NASH are very different from those of HBV- and HCV-chronic liver diseases. The prognosis of NASH is worse among
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Nonalcoholic steatohepatitis (NASH) is emerging worldwide because life-styles have changed to include much over-eating and less physical activity. The clinical and pathophysiological features of NASH are very different from those of HBV- and HCV-chronic liver diseases. The prognosis of NASH is worse among those with nonalcoholic fatty liver diseases (NAFLD), and some NASH patients show HCC with or without cirrhosis. In the present review we discuss fibrogenesis and the relationship between fibrosis and HCC occurrence in NASH to clarify the role of MMPs and TIMPs in both mechanisms. Previously we proposed MMP and TIMP expression in the multi-step occurrence of HCC from the literature based on viral-derived HCC. We introduce again these expressions during hepatocarcinogenesis and compare them to those in NASH-derived HCC, although the relationship with hepatic stem/progenitor cells (HPCs) invasion remains unknown. Signal transduction of MMPs and TIMPs is also discussed because it is valuable for the prevention and treatment of NASH and NASH-derived HCC. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Open AccessReview Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Prostate Cancer Progression
Cancers 2014, 6(3), 1298-1327; doi:10.3390/cancers6031298
Received: 4 April 2014 / Revised: 31 May 2014 / Accepted: 9 June 2014 / Published: 27 June 2014
Cited by 26 | PDF Full-text (721 KB) | HTML Full-text | XML Full-text
Abstract
Matrix metalloproteinases (MMPs), a group of zinc-dependent endopeptidases involved in the degradation of the extracellular matrix, play an important role in tissue remodeling associated with various physiological processes such as morphogenesis, angiogenesis, and tissue repair, as well as pathological processes including cirrhosis, arthritis
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Matrix metalloproteinases (MMPs), a group of zinc-dependent endopeptidases involved in the degradation of the extracellular matrix, play an important role in tissue remodeling associated with various physiological processes such as morphogenesis, angiogenesis, and tissue repair, as well as pathological processes including cirrhosis, arthritis and cancer. The MMPs are well established as mediators of tumor invasion and metastasis by breaking down connective tissue barriers. Although there has been a vast amount of literature on the role of MMPs in invasion, metastasis and angiogenesis of various cancers, the role of these endopeptidases in prostate cancer progression has not been systematically reviewed. This overview summarizes findings on the tissue and blood expression of MMPs, their function, regulation and prognostic implication in human prostate cancer, with a focus on MMP-2, -7, -9, MT1-MMP and tissue inhibitor of metalloproteinase 1 (TIMP-1). This review also summarizes the efficacy and failure of early-generation matrix metalloproteinase inhibitors (MMPIs) in the treatment of metastatic prostate cancer and highlights the lessons and challenges for next generation MMPIs. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Open AccessReview Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias
Cancers 2014, 6(2), 796-812; doi:10.3390/cancers6020796
Received: 12 December 2013 / Revised: 21 March 2014 / Accepted: 25 March 2014 / Published: 4 April 2014
Cited by 9 | PDF Full-text (691 KB) | HTML Full-text | XML Full-text
Abstract
Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their
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Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Figures

Open AccessReview MicroRNAs in the Regulation of MMPs and Metastasis
Cancers 2014, 6(2), 625-645; doi:10.3390/cancers6020625
Received: 8 January 2014 / Revised: 21 February 2014 / Accepted: 4 March 2014 / Published: 25 March 2014
Cited by 13 | PDF Full-text (578 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs are integral molecules in the regulation of numerous physiological cellular processes including cellular differentiation, proliferation, metabolism and apoptosis. Their function transcends normal physiology and extends into several pathological entities including cancer. The matrix metalloproteinases play pivotal roles, not only in tissue remodeling,
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MicroRNAs are integral molecules in the regulation of numerous physiological cellular processes including cellular differentiation, proliferation, metabolism and apoptosis. Their function transcends normal physiology and extends into several pathological entities including cancer. The matrix metalloproteinases play pivotal roles, not only in tissue remodeling, but also in several physiological and pathological processes, including those supporting cancer progression. Additionally, the contribution of active MMPs in metastatic spread and the establishment of secondary metastasis, via the targeting of several substrates, are also well established. This review focuses on the important miRNAs that have been found to impact cancer progression and metastasis through direct and indirect interactions with the matrix metalloproteinases. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Open AccessReview Monitoring and Inhibiting MT1-MMP during Cancer Initiation and Progression
Cancers 2014, 6(1), 416-435; doi:10.3390/cancers6010416
Received: 25 December 2013 / Revised: 7 February 2014 / Accepted: 8 February 2014 / Published: 17 February 2014
Cited by 23 | PDF Full-text (1017 KB) | HTML Full-text | XML Full-text
Abstract
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent type-I transmembrane metalloproteinase involved in pericellular proteolysis, migration and invasion. Numerous substrates and binding partners have been identified for MT1-MMP, and its role in collagenolysis appears crucial for tumor invasion. However, development of MT1-MMP inhibitors
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Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent type-I transmembrane metalloproteinase involved in pericellular proteolysis, migration and invasion. Numerous substrates and binding partners have been identified for MT1-MMP, and its role in collagenolysis appears crucial for tumor invasion. However, development of MT1-MMP inhibitors must consider the substantial functions of MT1-MMP in normal physiology and disease prevention. The present review examines the plethora of MT1-MMP activities, how these activities relate to cancer initiation and progression, and how they can be monitored in real time. Examination of MT1-MMP activities and cell surface behaviors can set the stage for the development of unique, selective MT1-MMP inhibitors. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Open AccessReview Matrix Metalloproteinases: The Gene Expression Signatures of Head and Neck Cancer Progression
Cancers 2014, 6(1), 396-415; doi:10.3390/cancers6010396
Received: 11 December 2013 / Revised: 14 January 2014 / Accepted: 29 January 2014 / Published: 13 February 2014
Cited by 11 | PDF Full-text (641 KB) | HTML Full-text | XML Full-text
Abstract
Extracellular matrix degradation by matrix metalloproteinases (MMPs) plays a pivotal role in cancer progression by promoting motility, invasion and angiogenesis. Studies have shown that MMP expression is increased in head and neck squamous cell carcinomas (HNSCCs), one of the most common cancers in
[...] Read more.
Extracellular matrix degradation by matrix metalloproteinases (MMPs) plays a pivotal role in cancer progression by promoting motility, invasion and angiogenesis. Studies have shown that MMP expression is increased in head and neck squamous cell carcinomas (HNSCCs), one of the most common cancers in the world, and contributes to poor outcome. In this review, we examine the expression pattern of MMPs in HNSCC by microarray datasets and summarize the current knowledge of MMPs, specifically MMP-1, -3, -7 -10, -12, -13, 14 and -19, that are highly expressed in HNSCCs and involved cancer invasion and angiogenesis. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Open AccessReview The Role of Matrix Metalloproteinases in Colorectal Cancer
Cancers 2014, 6(1), 366-375; doi:10.3390/cancers6010366
Received: 12 December 2013 / Revised: 24 January 2014 / Accepted: 26 January 2014 / Published: 10 February 2014
Cited by 21 | PDF Full-text (352 KB) | HTML Full-text | XML Full-text
Abstract
In the United States, colorectal cancer (CRC) is the third leading cause of cancer mortality, with limited treatment options for those with advanced disease. Matrix metalloproteinases (MMPs) are important for maintaining extracellular homeostasis but also play a prominent role in cancer cell invasion
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In the United States, colorectal cancer (CRC) is the third leading cause of cancer mortality, with limited treatment options for those with advanced disease. Matrix metalloproteinases (MMPs) are important for maintaining extracellular homeostasis but also play a prominent role in cancer cell invasion and dissemination. Expression levels of MMP-1, -2, -7, -9 and -13 correlate with worse outcomes; MMP-12 expression appears to be protective. Hence, MMPs are attractive therapeutic targets. Previous clinical trials using broad-spectrum MMP inhibitors were disappointing because of off-target toxicity and lack of efficacy. Now, the availability of safer, more selective inhibitors has renewed interest in therapeutic targeting of MMPs. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)
Open AccessReview Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression
Cancers 2014, 6(1), 240-296; doi:10.3390/cancers6010240
Received: 16 December 2013 / Revised: 20 January 2014 / Accepted: 21 January 2014 / Published: 27 January 2014
Cited by 27 | PDF Full-text (1198 KB) | HTML Full-text | XML Full-text
Abstract
Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many
[...] Read more.
Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many ways in which gelatinase B/MMP-9 influences tumour biology. Following a brief outline of the gelatinase B/MMP-9 gene and protein, we analyse the role(s) of gelatinase B/MMP-9 in different phases of the tumorigenic process, and compare the importance of gelatinase B/MMP-9 source in the carcinogenic process. What becomes apparent is the importance of inflammatory cell-derived gelatinase B/MMP-9 in tumour promotion, early progression and triggering of the “angiogenic switch”, the integral relationship between inflammatory, stromal and tumour components with respect to gelatinase B/MMP-9 production and activation, and the fundamental role for gelatinase B/MMP-9 in the formation and maintenance of tumour stem cell and metastatic niches. It is also apparent that gelatinase B/MMP-9 plays important tumour suppressing functions, producing endogenous angiogenesis inhibitors, promoting inflammatory anti-tumour activity, and inducing apoptosis. The fundamental roles of gelatinase B/MMP-9 in cancer biology underpins the need for specific therapeutic inhibitors of gelatinase B/MMP-9 function, the use of which must take into account and substitute for tumour-suppressing gelatinase B/MMP-9 activity and also limit inhibition of physiological gelatinase B/MMP-9 function. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Cancer Progress)

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