MMPs in Biology and Medicine

Jia, Di; Roy, Roopali; Moses, Marsha A.

doi:10.1002/9781118772287.ch10

Cited by 5 publications

(5 citation statements)

References 218 publications

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“…It has been proposed that EMT in cancer progression can be modulated by MMPs via different mechanisms: (1) EMT of epithelial cells can be directly induced by elevated levels of MMPs in the tumor microenvironment (Lochter et al, ; Sternlicht et al, ) and (2) initiation of invasion and metastasis is often accompanied by tumor cells undergoing EMT resulting in increased MMP levels (Radisky and Radisky, ). MMPs can promote the EMT process by cleaving, shedding, or degrading a variety of cell surface molecules (Jia et al, ). However, EMT can also be induced by proteins such as Annexin V (Tang et al, ), Snail (Zhao et al, ), or Bach 1 (Aletaha et al, ), which can regulate expression and/or activity of MMPs, thereby modulating the migratory phenotype involved in EMT.…”

Section: Functional Roles Of Mmps and Adams In The Tumor Microenvironmentioning

confidence: 99%

“…Given the important role of MMPs in different pathologies, there has been an increasing interest in the development of novel MMP‐specific molecular imaging techniques to detect and monitor the activity of these enzymes in different diseases. Many of the initial attempts to develop MMP‐specific imaging probes included fluorescent and bioluminescent probes for in vitro and in vivo detection and quantification of MMP activity that could potentially be correlated with disease progression (Bremer et al, , , ; Jia et al, ; Lee and Kim, ). The potential of these tracers has continued to be explored.…”

Section: Mmp‐specific Molecular Imagingmentioning

confidence: 99%

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Metalloproteinases and their roles in human cancer

Roy

Morad

Jedinak

et al. 2019

The Anatomical Record

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It is now widely appreciated that members of the matrix metalloproteinase (MMP) family of enzymes play a key role in cancer development and progression along with many of the hallmarks associated with them. The activity of these enzymes has been directly implicated in extracellular matrix remodeling, the processing of growth factors and receptors, the modulation of cell migration, proliferation, and invasion, the epithelial to mesenchymal transition, the regulation of immune responses, and the control of angiogenesis. Certain MMP family members have been validated as biomarkers of a variety of human cancers including those of the breast, brain, pancreas, prostate, ovary, and others. The related metalloproteinases, the A disintegrin and metalloproteinases (ADAMs), share a number of these functions as well. Here, we explore these essential metalloproteinases and some of their disease-associated activities in detail as well as some of their complementary translational potential. Anat Rec, 303:1557-1572, 2020.Matrix metalloproteinases (MMPs) are a multigene family of metal-dependent endopeptidases that play important and diverse roles in normal physiological and pathological processes. The classic domain structure of MMP family members can be found in Figure 1 (Roy et al., 2009). MMPs include an amino-terminal signal peptide required for secretion, a pro-domain that mediates latency via a cysteine-switch mechanism and a Zn 2+ -dependent catalytic domain that is responsible for enzymatic function. A majority of MMPs also contain a C-terminal hemopexinlike domain that provides substrate specificity. MMP activity is the rate-limiting step in extracellular matrix (ECM) degradation and it can regulate the activity of other proteases, growth factors, cytokines, and cell-surface ligands

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Section: Functional Roles Of Mmps and Adams In The Tumor Microenvironmentioning

confidence: 99%

Section: Mmp‐specific Molecular Imagingmentioning

confidence: 99%

Metalloproteinases and their roles in human cancer

Roy

Morad

Jedinak

et al. 2019

The Anatomical Record

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“…In this respect, matrix metalloproteinases (MMPs) are of particular interest. Originally thought to be associated exclusively with tissue remodelling and destruction, it is now widely appreciated that MMPs play a role in a variety of biological processes including cytokine and growth factor release, tumour growth and progression, angiogenesis and a number of inflammatory conditions . During the inflammatory response, MMPs and their complexes are released from connective tissue cells in response to pro‐inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel non‐invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network

et al. 2017

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Objective To examine a series of candidate markers for urological chronic pelvic pain syndrome (UCPPS), selected based on their proposed involvement in underlying biological processes so as to provide new insights into pathophysiology and suggest targets for expanded clinical and mechanistic studies. Methods Baseline urine samples from Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study participants with UCPPS (n = 259), positive controls (PCs; chronic pain without pelvic pain, n = 107) and healthy controls (HCs, n = 125) were analysed for the presence of proteins that are suggested in the literature to be associated with UCPPS. Matrix metalloproteinase (MMP)‐2, MMP‐9, MMP‐9/neutrophil gelatinase‐associated lipocalin (NGAL) complex (also known as Lipocalin 2), vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGF‐R1) and NGAL were assayed and quantitated using mono‐specific enzyme‐linked immunosorbent assays for each protein. Log‐transformed concentration (pg/mL or ng/mL) and concentration normalized to total protein (pg/μg) values were compared among the UCPPS, PC and HC groups within sex using the Student's t‐test, with P values adjusted for multiple comparisons. Multivariable logistic regression and receiver‐operating characteristic curves assessed the utility of the biomarkers in distinguishing participants with UCPPS and control participants. Associations of protein with symptom severity were assessed by linear regression. Results Significantly higher normalized concentrations (pg/μg) of VEGF, VEGF‐R1 and MMP‐9 in men and VEGF concentration (pg/mL) in women were associated with UCPPS vs HC. These proteins provided only marginal discrimination between UCPPS participants and HCs. In men with UCCPS, pain severity was significantly positively associated with concentrations of MMP‐9 and MMP‐9/NGAL complex, and urinary severity was significantly positively associated with MMP‐9, MMP‐9/NGAL complex and VEGF‐R1. In women with UCPPS, pain and urinary symptom severity were associated with increased normalized concentrations of MMP‐9/NGAL complex, while pain severity alone was associated with increased normalized concentrations of VEGF, and urinary severity alone was associated with increased normalized concentrations of MMP‐2. Pain severity in women with UCPPS was significantly positively associated with concentrations of all biomarkers except NGAL, and urinary severity with all concentrations except VEGF‐R1. Conclusion Altered levels of MMP‐9, MMP‐9/NGAL complex and VEGF‐R1 in men, and all biomarkers in women, were associated with clinical symptoms of UCPPS. None of the evaluated candidate markers usefully discriminated UCPPS patients from controls. Elevated VEGF, MMP‐9 and VEGF‐R1 levels in men and VEGF levels in women may provide potential new insights into the pathophysiology of UCPPS.

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“…It is a disease characterized by repeated seizures without any trigger 1 . Epilepsy encompasses a broad spectrum of conditions, with over 30 distinct epileptic syndromes and more than 15 types of seizures that have been recognized 2 . There are several causes of epilepsy, including traumatic brain injury, perinatal asphyxia, congenital abnormalities, genetic syndromes, brain infections, brain tumours, and stroke.…”

Section: Introductionmentioning

confidence: 99%

“…The use of organ-on-a-chip microfluidic devices, lined with living cells cultured under fluid flow, allows for the recapitulation of organ-level physiology and pathophysiology with high accuracy 6 . This innovative technology, which can recreate the physiological conditions and functionality of human organs on a microchip to model disease entities and test drugs, has the potential to significantly impact and streamline the process of drug development 2 . This technology holds great promise for substituting animals during the preclinical stages of pharmaceutical research and development.…”

Section: Introductionmentioning

confidence: 99%

Tailoring epilepsy treatment: personalized micro-physiological systems illuminate individual drug responses

Shariff,

Kantawala,

Xochitun Gopar Franco

et al. 2024

Annals of Medicine &Amp; Surgery

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Introduction: Approximately 50 million people worldwide have epilepsy, with many not achieving seizure freedom. Organ-on-chip technology, which mimics organ-level physiology, could revolutionize drug development for epilepsy by replacing animal models in preclinical studies. Our goal is to determine if customized micro-physiological systems can lead to tailored drug treatments for epileptic patients. Materials and methods: A comprehensive literature search was conducted utilizing various databases, including PubMed, Ebscohost, Medline, and the National Library of Medicine, using a predetermined search strategy. We focused on articles that addressed the role of personalized micro-physiological systems in individual drug responses and articles that discussed different types of epilepsy, diagnosis, and current treatment options. Additionally, articles that explored the components and design considerations of micro-physiological systems were reviewed to identify challenges and opportunities in drug development for challenging epilepsy cases. Results: The micro-physiological system offers a more accurate and cost-effective alternative to traditional models for assessing drug effects, toxicities, and disease mechanisms. Nevertheless, designing patient-specific models presents critical considerations, including the integration of analytical biosensors and patient-derived cells, while addressing regulatory, material, and biological complexities. Material selection, standardization, integration of vascular systems, cost efficiency, real-time monitoring, and ethical considerations are also crucial to the successful use of this technology in drug development. Conclusion: The future of organ-on-chip technology holds great promise, with the potential to integrate artificial intelligence and machine learning for personalized treatment for epileptic patients.

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MMPs in Biology and Medicine

Cited by 5 publications

References 218 publications

Metalloproteinases and their roles in human cancer

Metalloproteinases and their roles in human cancer

Identification of novel non‐invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network

Tailoring epilepsy treatment: personalized micro-physiological systems illuminate individual drug responses

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