Extracellular Matrix in the Regulation of Cellular Functions

2015 ◽  
pp. 88-98
Author(s):  
Erkki Ruoslahti
Keyword(s):  
Extracellular Matrix ◽  
Cellular Functions

scholarly journals Modulating Tumor Cell Functions by Tunable Nanopatterned Ligand Presentation

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Katharina Amschler ◽  
Michael P. Schön
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Cell Fate ◽  
Epithelial Mesenchymal Transition ◽  
Model Systems ◽  
Cellular Functions ◽  
Biophysical Parameters ◽  
Ligand Density ◽  
Mesenchymal Transition ◽  
Cell Functions

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.

scholarly journals The Role of the Extracellular Matrix Components in Cutaneous Wound Healing

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pawel Olczyk ◽  
Łukasz Mencner ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Wound Repair ◽  
Structural Integrity ◽  
Healing Process ◽  
Cellular Functions ◽  
Extracellular Matrix Components ◽  
Essential Components ◽  
Matrix Components

Wound healing is the physiologic response to tissue trauma proceeding as a complex pathway of biochemical reactions and cellular events, secreted growth factors, and cytokines. Extracellular matrix constituents are essential components of the wound repair phenomenon. Firstly, they create a provisional matrix, providing a structural integrity of matrix during each stage of healing process. Secondly, matrix molecules regulate cellular functions, mediate the cell-cell and cell-matrix interactions, and serve as a reservoir and modulator of cytokines and growth factors’ action. Currently known mechanisms, by which extracellular matrix components modulate each stage of the process of soft tissue remodeling after injury, have been discussed.

scholarly journals Regulation of cellular functions by extracellular matrix.

1992 ◽  
Vol 2 (10) ◽  
pp. S83 ◽  
Author(s):  
A Teti
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor Receptor ◽  
Matrix Proteins ◽  
Intercellular Spaces ◽  
Cellular Functions ◽  
Proliferation And Differentiation ◽  
Alpha Beta ◽  
Covalently Linked ◽  
Multicellular Organisms ◽  
Specific Ligand

Multicellular organisms are formed by specialized cells assembled in tissues. Individual cells contact and interact with other cells and with the extracellular matrix--a network of secreted proteins and carbohydrates that fills the intercellular spaces. The extracellular matrix helps cells to bind together and regulates a number of cellular functions, such as adhesion, migration, proliferation, and differentiation. It is formed by macromolecules, locally secreted by resident cells. The two main classes of macromolecules are polysaccharide glycosaminoglycans, usually covalently linked to proteins in the form of proteoglycans, and fibrous proteins of two functional types, structural (collagen, elastin) and adhesive (fibronectin, laminin, vitronectin, etc.). Receptors for extracellular matrix macromolecules are present in virtually all of the cells studied. They belong to the superfamily of integrins, alpha beta heterodimers, which, in most cases, recognize the Arg-Gly-Asp sequence of extracellular matrix proteins. On the exterior side of the cell, integrins link an extracellular matrix macromolecule, whereas in the cytosol, they bind the cytoskeleton, thereby forming a membrane bridge between extracellular and intracellular fibers. This structure enables the cell to adhere to the substratum. Similar to hormone- or growth factor-receptor binding, the interaction of the integrin with its specific ligand induces immediate signal transduction and influences cellular activities.

scholarly journals Distance-dependent adhesion of vascular cells on biofunctionalized nanostructures

2017 ◽  
Vol 3 (2) ◽  
pp. 683-686
Author(s):  
Sarah Biela ◽  
Britta Striegl ◽  
Kerstin Frey ◽  
Joachim P. Spatz ◽  
Ralf Kemkemer
Keyword(s):  
Extracellular Matrix ◽  
Vascular Tissue ◽  
Cell Types ◽  
Cell Interaction ◽  
Vascular Cells ◽  
Cellular Functions ◽  
Ligand Interaction ◽  
Nanostructured Surfaces ◽  
Peptide Motifs ◽  
Cell Cell

AbstractCell-cell and cell-extracellular matrix (ECM) adhesion regulates fundamental cellular functions and is crucial for cell-material contact. Adhesion is influenced by many factors like affinity and specificity of the receptor-ligand interaction or overall ligand concentration and density. To investigate molecular details of cell-ECM and cadherins (cell-cell) interaction in vascular cells functional nanostructured surfaces were used Ligand-functionalized gold nanoparticles (AuNPs) with 6-8 nm diameter, are precisely immobilized on a surface and separated by non-adhesive regions so that individual integrins or cadherins can specifically interact with the ligands on the AuNPs. Using 40 nm and 90 nm distances between the AuNPs and functionalized either with peptide motifs of the extracellular matrix (RGD or REDV) or vascular endothelial-cadherins (VEC), the influence of distance and ligand specificity on spreading and adhesion of endothelial cells (ECs) and smooth muscle cells (SMCs) was investigated. We demonstrate that RGD-dependent adhesion of vascular cells is similar to other cell types and that the distance dependence for integrin binding to ECM-peptides is also valid for the REDV motif. VEC-ligands decrease adhesion significantly on the tested ligand distances. These results may be helpful for future improvements in vascular tissue engineering and for development of implant surfaces.

scholarly journals Targeting heparin and heparan sulfate protein interactions

2017 ◽  
Vol 15 (27) ◽  
pp. 5656-5668 ◽  
Author(s):  
Ryan J. Weiss ◽  
Jeffrey D. Esko ◽  
Yitzhak Tor
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Protein Interactions ◽  
Human Disease ◽  
Binding Proteins ◽  
Cellular Functions ◽  
Animal Cells ◽  
Carbohydrate Chains

Heparan sulfate is ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These negatively-charged carbohydrate chains play essential roles in many important cellular functions by interacting with various heparan sulfate binding proteins (HSBP). This review discusses methods for targeting these complex biomolecules, as strategies for treating human disease.

Collagen Structure and Its Modifications at Different Diseases

2016 ◽  
Vol 2 (11) ◽  
Author(s):  
Natalia Lisitza
Keyword(s):  
Extracellular Matrix ◽  
Wide Spectrum ◽  
Dominant Role ◽  
Therapy Response ◽  
Structural Features ◽  
Collagen Structure ◽  
Cellular Functions ◽  
Collagen Types ◽  
Abnormal Expression ◽  
Polymeric Assemblies

<p>The collagen superfamily of proteins plays a dominant role in maintaining the integrity of various tissues and also has a number of other important functions. The superfamily includes more than 20 collagen types with altogether. Most collagens form polymeric assemblies. such as fibrils, networks and filaments, and the superfamily can be divided into several families based on these assemblies and structural features. The critical roles of collagens have been clearly illustrated by the wide spectrum of diseases caused by the mutations that occur in genes coding different collagen types. Collagens are also major components of the extracellular matrix (ECM). The abnormal expression, proteolysis and structure of these collagens influence cellular functions to elicit multiple effects on tumors, including proliferation, initiation, invasion, metastasis, and therapy response.</p>

scholarly journals Hyaluronan: Metabolism and Function

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1525 ◽  
Author(s):  
Takashi Kobayashi ◽  
Theerawut Chanmee ◽  
Naoki Itano
Keyword(s):  
Extracellular Matrix ◽  
Tissue Concentration ◽  
Molecular Size ◽  
Cellular Functions ◽  
Altered Expression ◽  
Surface Receptors ◽  
Hyaluronan Synthases ◽  
Wide Range ◽  
And Migration ◽  
And Function

As a major polysaccharide component of the extracellular matrix, hyaluronan plays essential roles in the organization of tissue architecture and the regulation of cellular functions, such as cell proliferation and migration, through interactions with cell-surface receptors and binding molecules. Metabolic pathways for biosynthesis and degradation tightly control the turnover rate, concentration, and molecular size of hyaluronan in tissues. Despite the relatively simple chemical composition of this polysaccharide, its wide range of molecular weights mediate diverse functions that depend on molecular size and tissue concentration. Genetic engineering and pharmacological approaches have demonstrated close associations between hyaluronan metabolism and functions in many physiological and pathological events, including morphogenesis, wound healing, and inflammation. Moreover, emerging evidence has suggested that the accumulation of hyaluronan extracellular matrix and fragments due to the altered expression of hyaluronan synthases and hyaluronidases potentiates cancer development and progression by remodeling the tumor microenvironment. In addition to the well-known functions exerted by extracellular hyaluronan, recent metabolomic approaches have also revealed that its synthesis can regulate cellular functions via the reprogramming of cellular metabolism. This review highlights the current advances in knowledge on the biosynthesis and catabolism of hyaluronan and describes the diverse functions associated with hyaluronan metabolism.

scholarly journals N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma

2019 ◽  
Vol 8 (9) ◽  
pp. 1303 ◽  
Author(s):  
Barnali Deb ◽  
Krishna Patel ◽  
Gajanan Sathe ◽  
Prashant Kumar
Keyword(s):  
Extracellular Matrix ◽  
Bladder Carcinoma ◽  
Molecular Subtype ◽  
Site Occupancy ◽  
Glycosylation Site ◽  
Protein Glycosylation ◽  
Protein Abundance ◽  
Cellular Functions ◽  
Cancer Subtypes ◽  
Matrix Organization

Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes. Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies. The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability. Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology. Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes. To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling. We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins. Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes. Most of the altered glycoproteins were also observed with changes in their global protein expression levels. However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes. Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma. N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype. These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.

scholarly journals Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm

2020 ◽  
Vol 318 (3) ◽  
pp. H652-H670 ◽  
Author(s):  
Bo Liu ◽  
David J. Granville ◽  
Jonathan Golledge ◽  
Zamaneh Kassiri
Keyword(s):  
Extracellular Matrix ◽  
Aortic Aneurysm ◽  
Aortic Rupture ◽  
Wall Structure ◽  
Pharmacological Treatments ◽  
Cellular Functions ◽  
The Past ◽  
Abdominal Aortic ◽  
Aneurysm Growth ◽  
Asymptomatic Disease

Aortic aneurysm is a permanent focal dilation of the aorta. It is usually an asymptomatic disease but can lead to sudden death due to aortic rupture. Aortic aneurysm-related mortalities are estimated at ∼200,000 deaths per year worldwide. Because no pharmacological treatment has been found to be effective so far, surgical repair remains the only treatment for aortic aneurysm. Aortic aneurysm results from changes in the aortic wall structure due to loss of smooth muscle cells and degradation of the extracellular matrix and can form in different regions of the aorta. Research over the past decade has identified novel contributors to aneurysm formation and progression. The present review provides an overview of cellular and noncellular factors as well as enzymes that process extracellular matrix and regulate cellular functions (e.g., matrix metalloproteinases, granzymes, and cathepsins) in the context of aneurysm pathogenesis. An update of clinical trials focusing on therapeutic strategies to slow abdominal aortic aneurysm growth and efforts underway to develop effective pharmacological treatments is also provided.

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