Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis

1999 ◽  
Vol 77 (7) ◽  
pp. 465-480 ◽  
Author(s):  
Marie-Annick Forget ◽  
Richard R Desrosiers ◽  
Richard Béliveau
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Connective Tissues ◽  
Cell Matrix ◽  
Physiological Processes ◽  
Matrix Interactions ◽  
Tumor Growth And Metastasis ◽  
Differentiation And Proliferation ◽  
Cell Matrix Interactions ◽  
Activation Cascade

Physiological processes involving remodelling of the extracellular matrix, such as wound healing, embryogenesis, angiogenesis, and the female reproductive cycle, require the activity of matrix metalloproteinases (MMPs). This group of proteases degrades basal membranes and connective tissues and plays an essential role in the homeostasis of the extracellular matrix. An imbalance in the expression or activity of MMPs can have important consequences in diseases such as multiple sclerosis, Alzheimer's disease, or the development of cancers. Because of the pathophysiological importance of MMPs, their activity is highly controlled in order to confine them to specific areas. An activation cascade, initiated by the proteolysis of plasminogen, cleaves proMMPs, and every step is controlled by specific activators or inhibitors. MMPs destabilize the organization of the extracellular matrix and influence the development of cancer by contributing to cell migration, tumor cell proliferation, and angiogenesis. Accordingly, these proteases possess an important role in cell-matrix interactions by affecting fundamental processes such as cell differentiation and proliferation. Therefore, the characterization of MMPs involved in specific types and stages of tumors will significantly improve the diagnosis and treatment of these cancers in humans.Key words: matrix metalloproteinases, physiology, cancer, cell invasion, extracellular matrix.

Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Gelatinase A ◽  
Cellular Mechanisms ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Matrix ◽  
Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

scholarly journals A computational framework for modeling cell–matrix interactions in soft biological tissues

2021 ◽  
Author(s):  
Jonas F. Eichinger ◽  
Maximilian J. Grill ◽  
Iman Davoodi Kermani ◽  
Roland C. Aydin ◽  
Wolfgang A. Wall ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Three Dimensional ◽  
Biological Tissues ◽  
Computational Framework ◽  
Cell Matrix ◽  
Physiological Processes ◽  
Matrix Interactions ◽  
Mechanical Homeostasis ◽  
Cell Matrix Interactions ◽  
Short Time

AbstractLiving soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.

scholarly journals Extracellular Matrix Hydrogels Promote Expression of Paxillin, a Muscle-Tendon Junction Marker

2021 ◽  
Author(s):  
Lewis S. Gaffney ◽  
Matthew B. Fisher ◽  
Donald O. Freytes
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Conditioned Media ◽  
Type I ◽  
Tissue Specific ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Tissue Models ◽  
Cells Cultured

AbstractMuscle and tendon injuries are prevalent and range from minor sprains and strains to traumatic, debilitating injuries. However, the interactions between these tissues during injury and recovery remain unclear. Three-dimensional tissue models that incorporate both tissues and a physiologically relevant junction between muscle and tendon may aide in understanding how the two tissues interact. Here, we use tissue specific extracellular matrix (ECM) derived from muscle and tendon to determine how cells of each tissue interact with the microenvironment of the opposite tissue resulting in junction specific features. ECM materials were derived from the achilles tendon and gastrocnemius muscle, decellularized, and processed to form tissue specific pre-hydrogel digests. C2C12 myoblasts and tendon fibroblasts were cultured in tissue-specific ECM conditioned media or encapsulated in tissue-specific ECM hydrogels to determine cell-matrix interactions and the effects on a muscle-tendon junction marker, paxillin. ECM conditioned media had only a minor effect on upregulation of paxillin in cells cultured in monolayer. However, cells cultured within ECM hydrogels had 50-70% higher paxillin expression than cells cultured in type I collagen hydrogels. Contraction of the ECM hydrogels varied by the type of ECM used. Subsequent experiments with varying density of type I collagen (and thus contraction) showed no correlation between paxillin expression and the amount of gel contraction, suggesting that a constituent of the ECM was the driver of paxillin expression in the ECM hydrogels. Using tissue specific ECM allowed for the de-construction of the cell-matrix interactions similar to muscle-tendon junctions to study the expression of MTJ specific proteins.Impact StatementThe muscle-tendon junction is an important feature of muscle-tendon units; however, despite cross-talk between the two tissue types, it is overlooked in current research. Deconstructing the cell-matrix interactions will allow the opportunity to study significant junction specific features and markers that should be included in tissue models of the muscle-tendon unit, while gaining a deeper understanding of the natural junction. This research aims to inform future methods to engineer a more relevant multi-tissue platform to study the muscle-tendon unit.

scholarly journals Concepts of extracellular matrix remodelling in tumour progression and metastasis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Juliane Winkler ◽  
Abisola Abisoye-Ogunniyan ◽  
Kevin J. Metcalf ◽  
Zena Werb
Keyword(s):  
Extracellular Matrix ◽  
Tumour Progression ◽  
Metastatic Progression ◽  
Cell Matrix ◽  
Bidirectional Communication ◽  
Growth Increase ◽  
Matrix Interactions ◽  
Extracellular Matrix Remodelling ◽  
Underlying Mechanisms ◽  
Cell Matrix Interactions

Abstract Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM. These tumour-driven changes support tumour growth, increase migration of tumour cells, and remodel the ECM in distant organs to allow for metastatic progression. A better understanding of the underlying mechanisms of tumourigenic ECM remodelling is crucial for developing therapeutic treatments for patients.

Morphogenese proteins from dentine extracellular matrix and cell-Matrix interactions

1991 ◽  
Vol 19 (2) ◽  
pp. 187S-187S ◽  
Author(s):  
ANTHONY J SMITH ◽  
ROSALIND S TOBIAS ◽  
CLIVE G PLANT ◽  
ROGER M BROWNE ◽  
HERVE LESOT ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

Regional-specific meniscal extracellular matrix hydrogels and their effects on cell-matrix interactions of fibrochondrocytes

2021 ◽  
Author(s):  
Jinglei Wu ◽  
Jiazhu Xu ◽  
Yi-hui Huang ◽  
Liping Tang ◽  
Yi Hong
Keyword(s):  
Extracellular Matrix ◽  
Compressive Strength ◽  
Invasive Treatment ◽  
Pepsin Digestion ◽  
Cell Behaviors ◽  
Biochemical Effects ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Biochemical Variation ◽  
Cell Matrix Interactions

Abstract Decellularized meniscal extracellular matrix (ECM) material holds great potential for meniscus repair and regeneration. Particularly, injectable ECM hydrogel is highly desirable for the minimally invasive treatment of irregularly shaped defects. Although regional-specific variations of the meniscus are well documented, no ECM hydrogel has been reported to simulate zonally specific microenvironments of the native meniscus. To fill the gap, different (outer, middle, and inner) zones of porcine menisci were separately decellularized. Then the regionally decellularized meniscal ECMs were solubilized by pepsin digestion, neutralized, and then form injectable hydrogels. The hydrogels were characterized in gelation behaviors and mechanical properties and seeded with bovine fibrochondrocytes to evaluate the regionally biochemical effects on the cell-matrix interactions. Our results showed that the decellularized inner meniscal ECM (IM) contained the greatest glycosaminoglycan (GAG) content and the least collagen content compared with the decellularized outer meniscal ECM (OM) and middle meniscal ECM (MM). The IM hydrogel showed lower compressive strength than the OM hydrogel. When encapsulated with fibrochondrocytes, the IM hydrogel accumulated more GAG, contracted to a greater extent and reached higher compressive strength than that of the OM hydrogel at 28 days. Our findings demonstrate that the regionally specific meniscal ECMs present biochemical variation and show various effects on the cell behaviors, thus providing information on how meniscal ECM hydrogels may be utilized to reconstruct the microenvironments of the native meniscus.

Extracellular matrix remodeling—Methods to quantify cell–matrix interactions

Biomaterials ◽  
2007 ◽  
Vol 28 (2) ◽  
pp. 151-161 ◽  
Author(s):  
Leah C. Abraham ◽  
J. Fred Dice ◽  
Patrick F. Finn ◽  
Nicholas T. Mesires ◽  
Kyongbum Lee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

scholarly journals The Distribution of the Matricellular Protein Thrombospondin 2 in Tissues of Embryonic and Adult Mice

1998 ◽  
Vol 46 (9) ◽  
pp. 1007-1015 ◽  
Author(s):  
Themis R. Kyriakides ◽  
Yu-Hong Zhu ◽  
Zhantao Yang ◽  
Paul Bornstein
Keyword(s):  
Articular Chondrocytes ◽  
Dermal Fibroblasts ◽  
Matricellular Protein ◽  
Vascular Density ◽  
Null Mouse ◽  
Connective Tissues ◽  
Cell Matrix ◽  
Adult Tissues ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

Mice that lack the matricellular protein thrombospondin 2 (TSP2) develop a pleiotropic phenotype characterized by morphological changes in connective tissues, an increase in vascular density, and a propensity for bleeding. Furthermore, dermal cells derived from TSP2-null mice display adhesion defects, a finding that implicates TSP2 in cell-matrix interactions. To gain a better understanding of the participation of TSP2 in the development and maturation of the mouse, we examined its distribution in embryonic and adult tissues. Special attention was paid to the presence of TSP2 in collagen fibers, because collagen fibrils in the TSP2-null mouse appear to be irregular in size and contour by electron microscopy. Immunohistochemical analysis of Day 15 and Day 18 embryos revealed TSP2 in areas of chondrogenesis, osteogenesis, and vasculogenesis, and in dermal and other connective tissue-forming cells. Distinctly different patterns of deposition of TSP2 were observed in areas of developing cartilage and bone at Days 15 and 18 of embryonic development. A survey of adult tissues revealed TSP2 in dermal fibroblasts, articular chondrocytes, Purkinje cells in the cerebellum, Leidig cells in the testis, and in the adrenal cortex. Dermal fibroblasts were also shown to synthesize TSP2 in vitro. The distribution of TSP2 during development is in keeping with its participation in the formation of a variety of connective tissues. In adult tissues, TSP2 is located in the pericellular environment, where it can potentially influence the cell-matrix interactions associated with cell movement and tissue repair.

scholarly journals Induction of Caspase-Mediated Cell Death by Matrix Metalloproteinases in Cerebral Endothelial Cells after Hypoxia—Reoxygenation

2004 ◽  
Vol 24 (7) ◽  
pp. 720-727 ◽  
Author(s):  
Sun-Ryung Lee ◽  
Eng H. Lo
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Matrix Metalloproteinases ◽  
Caspase 3 ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Endothelial Cell Death ◽  
Cell Matrix Interactions ◽  
Hypoxia Reoxygenation

Matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral ischemia by degrading matrix components in the neurovascular unit. In this study, the authors document a pathway by which MMPs interfere with cell—matrix interactions and trigger caspase-mediated cytotoxicity in brain endothelial cells. Hypoxia—reoxygenation induced endothelial cytotoxicity. Cytoprotection with zDEVD-fmk confirmed that cell death was partly caspase mediated. The temporal profile of caspase-3 activation was matched by elevations in MMP-2 and MMP-9. MMP inhibitors significantly decreased caspase-3 activation and reduced endothelial cell death. Degradation of matrix fibronectin confirmed the presence of extracellular proteolysis. Increasing integrin-linked kinase signaling with the β1 integrin-activating antibody (8A2) ameliorated endothelial cytotoxicity. The results suggest that MMP-9 and MMP-2 contribute to caspase-mediated brain endothelial cell death after hypoxia—reoxygenation by disrupting cell—matrix interactions and homeostatic integrin signaling.

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