Variants of integrin β4 subunit in human endometrial adenocarcinoma cells: mediators of ECM-induced differentiation?

1996 ◽  
Vol 74 (6) ◽  
pp. 867-873 ◽  
Author(s):  
Elisabeth Strunck ◽  
Gunter Vollmer
Keyword(s):  
Extracellular Matrix ◽  
Endometrial Adenocarcinoma ◽  
Tumor Development ◽  
Functional Differentiation ◽  
Cell Matrix ◽  
Integrin Β4 ◽  
The Matrix ◽  
And Function ◽  
Cell Matrix Interactions

The influence of extracellular matrix (ECM) on expression and function of integrins in carcinogenesis and differentiation is not well understood, but the importance of altered adhesion features for tumor development and progression is obvious. Integrins as versatile molecules are mainly responsible for mediating cell–matrix interactions and transmembrane signal transduction. They are capable of transducing outside-in signals from ECM components or conversely to organize the matrix by inside-out signaling. In the study presented here, we report that the reconstituted basement membrane, Matrigel™, which induces morphological and functional differentiation of the endometrial adenocarcinoma cell line HEC 1B(L), also regulates the expression of various forms of the integrin β4 subunit. Furthermore, we were able to identify full-length isoforms with and without an altered cytoplasmic domain as well as truncated forms. Our findings suggest a regulatory role of integrin β4 isoforms and fragments in the process of in vitro differentiation of HEC 1B(L).Key words: endometrium, tumor cells, differentiation, extracellular matrix, β4-integrin expression.

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.

P0658MATRIX AND FLOW MODULATE GENE EXPRESSION IN A 3D VASCULARISED TUBULE MODEL

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Julie Williams ◽  
Sanlin Robinson ◽  
Babak Alaei ◽  
Kimberly Homan ◽  
Maryam Clausen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Impact Analysis ◽  
Cell Types ◽  
Drug Uptake ◽  
Shear Stresses ◽  
The Matrix ◽  
And Function

Abstract Background and Aims Questions abound regarding the translation of in vitro 2D cell culture systems to the human setting. This is especially true of the kidney in which there is a complex hierarchical structure and a multitude of cell types. While it is well accepted that extracellular matrix plays a large part in directing cellular physiology emerging research has highlighted the importance of shear stresses and flow rates too. To fully recapitulate the normal gene expression and function of a particular renal cell type how important is it to completely reconstitute their in vivo surroundings? Method To answer this question, we have cultured proximal tubular (PT) epithelial cells in a 3-dimensional channel embedded within an engineered extracellular matrix (ECM) under physiological flow that is colocalised with an adjacent channel lined with renal microvascular endothelial cells that mimic a peritubular capillary. Modifications to the system were made to allow up to 12 chips to be run in parallel in an easily handleable form. After a period of maturation under continuous flow, both cell types were harvested for RNAseq analyses. RNA expression data was compared with cells cultured under static 2-dimensional conditions on plastic or the engineered ECM. Additionally, the perfusion of glucose through this 3D vascularised PT model has been investigated in the presence and absence of known diabetes modulating agents. Results PCA of RNAseq data showed that a) static non-coated, b) static matrix-coated and c) flow matrix-coated conditions separated into 3 distinct groups, while cell co-culture had less impact. Analysis of transcriptomic signatures showed that many genes were modulated by the matrix with additional genes influenced under flow conditions. Several of these genes, classified as transporters, are of particular importance when using this model to assess drug uptake and safety implications. Co-culture regulated some interesting genes, but fewer than anticipated. Preliminary experiments are underway to monitor glucose uptake and transport between tubules under different conditions. Conclusion We have developed a medium throughput system in which matrix and flow modulate gene expression. This system can be used to study the physiology of molecular cross-talk between cells. Ongoing analysis will further consider relevance to human physiology.

Emerging concepts in cardiac matrix biologyThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

2009 ◽  
Vol 87 (12) ◽  
pp. 996-1008 ◽  
Author(s):  
Leon Espira ◽  
Michael P. Czubryt
Keyword(s):  
Cardiac Development ◽  
Cardiac Fibroblasts ◽  
Dynamic Network ◽  
Support Structure ◽  
Cardiovascular Research ◽  
Cell Matrix ◽  
The Matrix ◽  
And Function ◽  
Cell Matrix Interactions ◽  
And Behavior

The cardiac extracellular matrix, far from being merely a static support structure for the heart, is now recognized to play central roles in cardiac development, morphology, and cell signaling. Recent studies have better shaped our understanding of the tremendous complexity of this active and dynamic network. By activating intracellular signal cascades, the matrix transduces myocardial physical forces into responses by myocytes and fibroblasts, affecting their function and behavior. In turn, cardiac fibroblasts and myocytes play active roles in remodeling the matrix. Coupled with the ability of the matrix to act as a dynamic reservoir for growth factors and cytokines, this interplay between the support structure and embedded cells has the potential to exert dramatic effects on cardiac structure and function. One of the clearest examples of this occurs when cell–matrix interactions are altered inappropriately, contributing to pathological fibrosis and heart failure. This review will examine some of the recent concepts that have emerged regarding exactly how the cardiac matrix mediates these effects, how our collective vision of the matrix has changed as a result, and the current state of attempts to pharmacologically treat fibrosis.

scholarly journals Regenerative properties of human extraembryonal organs in tissue engineering

2018 ◽  
Vol 20 (4) ◽  
pp. 192-198
Author(s):  
L I Kalyuzhnaya ◽  
O N Kharkevich ◽  
A A Schmidt ◽  
O V Protasov
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Umbilical Cord ◽  
Current Knowledge ◽  
Biological Properties ◽  
Engineering Structures ◽  
The Matrix ◽  
Cell Growth And Differentiation ◽  
And Function ◽  
Cell Matrix Interactions

The characteristics of the umbilical cord extracellular matrix are discussed relatively of their potential use for tissue engineering. The purpose of this review is to assess the current knowledge about using of homologous biomaterials with regenerative properties to create bioengineered structures. One of the most important components of tissue engineering - matrix (scaffold), resident cells can migrate, attach to it and function. Due to their structure, matrices should be easily integrated into the patient’s tissue and provide conditions for cell growth and differentiation. The cells that populate the matrix in the bioreactor before the transplantation of this construction, or resident cells recruited into the transplanted extracellular matrix), and cell- matrix interactions are absolutely necessary components of tissue engineering. Available commercial bioengineering products made from mammalian tissues have certain advantages and significant disadvantages due to the risks of immunological reactions and transmission of infectious agents. The transplantation of products from xenogenic materials is prohibited by law in the Russian Federation. The donor material is limited, receipt of human cadaver material requires a long period of legal registration, which has a detrimental effect on the biomaterial. Therefore, finding a suitable homologous biomaterial is ongoing. Due to the peculiarities of the embryonic phenotype, extraembryonic tissues have special biological properties, one of which is the scarless healing of wounds. Low immunogenicity, optimal mechanical properties of extracellular matrix, presence of cell adhesion molecules and growth factors promoting regeneration provide anti-inflammatory, anti-fibrotic, anti- scarring properties for tissue engineering structures from umbilical cord and amniotic membrane. Umbilical cord and amnion due to the availability and non-invasiveness of obtaining from healthy young donors are an excellent source of homologous biomaterial for extracting matrices, cells and hydrogels for tissue engineering and regenerative medicine.

scholarly journals Mechanical Interaction of Angiogenic Microvessels With the Extracellular Matrix

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Lowell T. Edgar ◽  
James B. Hoying ◽  
Urs Utzinger ◽  
Clayton J. Underwood ◽  
Laxminarayanan Krishnan ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Blood Vessels ◽  
Element Model ◽  
Mechanical Interaction ◽  
Matrix Mechanics ◽  
Two Photon ◽  
Cell Matrix ◽  
Vascular Elements ◽  
The Matrix

Angiogenesis is the process by which new blood vessels sprout from existing blood vessels, enabling new vascular elements to be added to an existing vasculature. This review discusses our investigations into the role of cell-matrix mechanics in the mechanical regulation of angiogenesis. The experimental aspects of the research are based on in vitro experiments using an organ culture model of sprouting angiogenesis with the goal of developing new treatments and techniques to either promote or inhibit angiogenic outgrowth, depending on the application. Computational simulations were performed to simulate angiogenic growth coupled to matrix deformation, and live two-photon microscopy was used to obtain insight into the dynamic mechanical interaction between angiogenic neovessels and the extracellular matrix. In these studies, we characterized how angiogenic neovessels remodel the extracellular matrix (ECM) and how properties of the matrix such as density and boundary conditions influence vascular growth and alignment. Angiogenic neovessels extensively deform and remodel the matrix through a combination of applied traction, proteolytic activity, and generation of new cell-matrix adhesions. The angiogenic phenotype within endothelial cells is promoted by ECM deformation and remodeling. Sensitivity analysis using our finite element model of angiogenesis suggests that cell-generated traction during growth is the most important parameter controlling the deformation of the matrix and, therefore, angiogenic growth and remodeling. Live two-photon imaging has also revealed numerous neovessel behaviors during angiogenesis that are poorly understood such as episodic growth/regression, neovessel colocation, and anastomosis. Our research demonstrates that the topology of a resulting vascular network can be manipulated directly by modifying the mechanical interaction between angiogenic neovessels and the matrix.

scholarly journals Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Wound Repair ◽  
Enzyme Activation ◽  
Processing Enzymes ◽  
The Matrix ◽  
Signaling Receptors ◽  
State Of Rest ◽  
And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

Recent Advances in Biohybrid Materials for Tissue Engineering and Regenerative Medicine

2016 ◽  
Vol 04 (01) ◽  
pp. 1640001 ◽  
Author(s):  
Ying Wan ◽  
Xing Li ◽  
Shenqi Wang
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Cell Function ◽  
Rapid Prototype ◽  
Artificial Organs ◽  
Specific Cell ◽  
Cell Matrix ◽  
Matrix Surface ◽  
The Matrix ◽  
Cell Matrix Interactions

Biohybrid materials play an important role in tissue engineering, artificial organs and regenerative medicine due to their regulation of cell function through specific cell–matrix interactions involving integrins, mostly those of fibroblasts and myofibroblasts, and ligands on the matrix surface, which have become current research focus. In this paper, recent progress of biohybrid materials, mainly including main types of biohybrid materials, rapid prototype (RP) technique for construction of 3D biohybrid materials, was reviewed in detail; moreover, their applications in tissue engineering, artificial organs and regenerative medicine were also reviewed in detail. At last, we address the challenges biohybrid materials may face.

The extracellular matrix of the developing cornea: diversity, deposition and function*

Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 195-205
Author(s):  
J. B. L. Bard ◽  
M. K. Bansal ◽  
A. S. A. Ross
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulphate ◽  
Corneal Stroma ◽  
Experimental System ◽  
Collagen I ◽  
And Function ◽  
20 Nm

This paper examines the role of the extracellular matrix (ECM) in the development of the cornea. After a brief summary of the corneal structure and ECM, we describe evidence suggesting that the differentiation of neural crest (NC) cells into endothelium and fibroblasts is under the control of ocular ECM. We then examine the role of collagen I in stromal morphogenesis by comparing normal corneas with those of homozygous Movl3 mice which do not make collagen I. We report that, in spite of this absence, the cellular morphology of the Movl3 eye is indistinguishable from that of the wild type. In the 16-day mutant stroma, however, the remaining collagens form small amounts of disorganized, thin fibrils rather than orthogonally organized 20 nm-diameter fibrils; a result implying that collagen I plays only a structural role and that its absence is not compensated for. It also suggests that, because these remaining collagens will not form the normal fibrils that they will in vitro, fibrillogenesis in the corneal stroma differs from that elsewhere. The latter part of the paper describes our current work on chick stromal deposition using corneal epithelia isolated with an intact basal lamina that lay down in vitro ∼3μm-thick stromas of organized fibrils similar to that seen in vivo. This experimental system has yielded two unexpected results. First, the amount of collagen and proteoglycans produced by such epithelia is not dependent on whether its substratum is collagenous and we therefore conclude that stromal production by the intact epithelium is more autonomous than hitherto thought. Second, chondroitin sulphate (CS), the predominant proteoglycan, appears to play no role in stromal morphogenesis: epithelia cultured in testicular hyaluronidase, which degrades CS, lay down stromas whose organization and fibrildiameter distribution are indistinguishable from controls. One possible role for CS, however, is as a lubricant which facilitates corneal growth: it could allow fibrils to move over one another without deforming their orthogonal organization. Finally, we have examined the processes of fibrillogenesis in the corneal stroma and conclude that they are different from those elsewhere in the embryo and in vitro, perhaps because there is in the primary stroma an unidentified, highly hydrated ECM macromolecule that embeds the fibrils and that may mediate their morphogenesis.

scholarly journals Imaging and Analysis of Cellular Locations in Three-Dimensional Tissue Models

2019 ◽  
Vol 25 (3) ◽  
pp. 753-761 ◽  
Author(s):  
Warren Colomb ◽  
Matthew Osmond ◽  
Charles Durfee ◽  
Melissa D. Krebs ◽  
Susanta K. Sarkar
Keyword(s):  
Three Dimensional ◽  
Human Mesenchymal Stem Cells ◽  
Basic Research ◽  
Light Sheet ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Tissue Models ◽  
Alginate Matrix

AbstractThe absence of quantitative in vitro cell–extracellular matrix models represents an important bottleneck for basic research and human health. Randomness of cellular distributions provides an opportunity for the development of a quantitative in vitro model. However, quantification of the randomness of random cell distributions is still lacking. In this paper, we have imaged cellular distributions in an alginate matrix using a multiview light sheet microscope and developed quantification metrics of randomness by modeling it as a Poisson process, a process that has constant probability of occurring in space or time. We imaged fluorescently labeled human mesenchymal stem cells embedded in an alginate matrix of thickness greater than 5 mm with $\sim\! {\rm 2}{\rm. 9} \pm {\rm 0}{\rm. 4}\,\mu {\rm m}$ axial resolution, the mean full width at half maximum of the axial intensity profiles of fluorescent particles. Simulated randomness agrees well with the experiments. Quantification of distributions and validation by simulations will enable quantitative study of cell–matrix interactions in tissue models.

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