scholarly journals The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Maricela Maldonado ◽  
Jin Nam
Keyword(s):  
Extracellular Matrix ◽  
Repair Process ◽  
Cellular Component ◽  
Ecm Remodeling ◽  
Multiple Factors ◽  
Inflammatory Conditions ◽  
Composition And Structure ◽  
Poor Understanding ◽  
Wear And Tear

Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA.

scholarly journals The Role of Extracellular Vesicles in the Progression of Tumors towards Metastasis

2021 ◽  
Author(s):  
Bhaskar Basu ◽  
Subhajit Karmakar
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Lipid Membrane ◽  
Recipient Cell ◽  
Ecm Remodeling ◽  
Secondary Tumor ◽  
Metastatic Cells

Extracellular vesicles (EVs) are cell-derived lipid membrane bound vesicles that serve as mediators of intercellular communication. EVs have been found to regulate a wide range of cellular processes through the transference of genetic, protein and lipid messages from the host cell to the recipient cell. Unsurprisingly, this major mode of intracellular communication would be abrogated in cancer. Ever increasing evidence points towards a key role of EVs in promoting tumor development and in contributing to the various stages of metastasis. Tumor released EVs have been shown to facilitate the transference of oncogenic proteins and nucleic acids to other tumor cells and to the surrounding stromal cells, thereby setting up a tumor permissive microenvironment. EVs released from tumor cells have been shown to promote extracellular matrix (ECM) remodeling through the modulation of neighboring tumor cells and stromal cells. EVs released from disseminated tumor cells have been reported to attract circulating tumor cells (CTCs) via chemotaxis and induce the production of specific extracellular matrix components from neighboring stromal cells so as to support the growth of metastatic cells at the secondary tumor site. Circulating levels of tumor derived EVs of patients have been correlated with incidence of metastasis and disease relapse.

scholarly journals Cancer Cell-derived Secretory Factors in Breast Cancer-associated Lung Metastasis: Their Mechanism and Future Prospects

2020 ◽  
Vol 20 (3) ◽  
pp. 168-186 ◽  
Author(s):  
Tabinda Urooj ◽  
Bushra Wasim ◽  
Shamim Mushtaq ◽  
Syed Nudrat Nawaid Shah ◽  
Muzna Shah
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Primary Site ◽  
Ecm Remodeling ◽  
Metastatic Cells ◽  
Extracellular Matrix Components ◽  
Matrix Components

: In Breast cancer, Lung is the second most common site of metastasis after the bone. Various factors are responsible for Lung metastasis occurring secondary to Breast cancer. Cancer cellderived secretory factors are commonly known as ‘Cancer Secretomes’. They exhibit a prompt role in the mechanism of Breast cancer lung metastasis. They are also major constituents of hostassociated tumor microenvironment. Through cross-talk between cancer cells and the extracellular matrix components, cancer cell-derived extracellular matrix components (CCECs) such as hyaluronan, collagens, laminin and fibronectin cause ECM remodeling at the primary site (breast) of cancer. However, at the secondary site (lung), tenascin C, periostin and lysyl oxidase, along with pro-metastatic molecules Coco and GALNT14, contribute to the formation of pre-metastatic niche (PMN) by promoting ECM remodeling and lung metastatic cells colonization. Cancer cell-derived secretory factors by inducing cancer cell proliferation at the primary site, their invasion through the tissues and vessels and early colonization of metastatic cells in the PMN, potentiate the mechanism of Lung metastasis in Breast cancer. : On the basis of biochemical structure, these secretory factors are broadly classified into proteins and non-proteins. This is the first review that has highlighted the role of cancer cell-derived secretory factors in Breast cancer Lung metastasis (BCLM). It also enumerates various researches that have been conducted to date in breast cancer cell lines and animal models that depict the prompt role of various types of cancer cell-derived secretory factors involved in the process of Breast cancer lung metastasis. In the future, by therapeutically targeting these cancer driven molecules, this specific type of organ-tropic metastasis in breast cancer can be successfully treated.

scholarly journals Interplay of TGFb superfamily members governs optic fissure closure

2014 ◽  
Author(s):  
Stephan Heermann ◽  
Priska Eckert ◽  
Juan L Mateo ◽  
Eleni Roussa ◽  
Belal Rahhal ◽  
...  
Keyword(s):  
Bmp Signaling ◽  
Microarray Data Analysis ◽  
Actual Process ◽  
Ecm Remodeling ◽  
Multiple Factors ◽  
Bmp Antagonists ◽  
Vertebrate Eye ◽  
Tgfb Signaling ◽  
Development Proceeds

The optic fissure is a gap in the developing vertebrate eye and must be closed as development proceeds. A persisting optic fissure is referred to as coloboma, a major cause for blindness in children. Multiple factors have been linked to coloboma formation, however, the actual process of fissure closure is only poorly understood. Based on our findings we propose an important role of TGFb signaling for optic fissure closure. We show active TGFb signaling in the fissure margins, analyzed by a new TGFb signaling reporter zebrafish. We found BMP antagonists regulated by TGFb. These antagonists we also found expressed in the fissure margins. Finally we show a coloboma phenotype in a TGFb KO mouse. Microarray data analysis indicates intense TGFb dependent remodeling of the extracellular matrix (ECM) during optic fissure closure. We propose that TGFb is driving optic fissure closure by ECM remodeling. As previously shown, inhibition of BMP signaling is important for such TGFb dependent ECM remodeling. We show that this is achieved by the regulation of BMP antagonists, expressed in the optic fissure margins.

scholarly journals Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases

2019 ◽  
Vol 20 (19) ◽  
pp. 4888 ◽  
Author(s):  
Ruiz-Ojeda ◽  
Méndez-Gutiérrez ◽  
Aguilera ◽  
Plaza-Díaz
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Tissue Expansion ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Survival And Development ◽  
Tissue Receptors

The extracellular matrix (ECM) is a network of different proteins and proteoglycans that controls differentiation, migration, repair, survival, and development, and it seems that its remodeling is required for healthy adipose tissue expansion. Obesity drives an excessive lipid accumulation in adipocytes, which provokes immune cells infiltration, fibrosis (an excess of deposition of ECM components such as collagens, elastin, and fibronectin) and inflammation, considered a consequence of local hypoxia, and ultimately insulin resistance. To understand the mechanism of this process is a challenge to treat the metabolic diseases. This review is focused at identifying the putative role of ECM in adipose tissue, describing its structure and components, its main tissue receptors, and how it is affected in obesity, and subsequently the importance of an appropriate ECM remodeling in adipose tissue expansion to prevent metabolic diseases.

scholarly journals Extracellular Matrix Component Remodeling in Respiratory Diseases: What Has Been Found in Clinical and Experimental Studies?

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 342 ◽  
Author(s):  
Juliana T. Ito ◽  
Juliana D. Lourenço ◽  
Renato F. Righetti ◽  
Iolanda F.L.C. Tibério ◽  
Carla M. Prado ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Function ◽  
Respiratory Diseases ◽  
Structural Changes ◽  
Experimental Studies ◽  
Experimental Models ◽  
Airway Hyperreactivity ◽  
Chronic Obstructive ◽  
Ecm Remodeling ◽  
Inflammatory Conditions

Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function. In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity. In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression. In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive care unit. This review uses experimental models and human studies to describe how inflammatory conditions and ECM remodeling contribute to the loss of lung function in these respiratory diseases.

scholarly journals The Importance of the Extracellular Matrix in HPV-Associated Diseases

2021 ◽  
Author(s):  
Joana Sampaio ◽  
Joana Ferreira ◽  
Ana Carolina Santos ◽  
Manuel Bicho ◽  
Maria Clara Bicho
Keyword(s):  
Extracellular Matrix ◽  
Sexually Transmitted Diseases ◽  
Hpv Infection ◽  
Cellular Component ◽  
Sexually Transmitted ◽  
Papillomavirus Infection ◽  
Proliferation And Apoptosis ◽  
Malignant Lesions ◽  
Dynamic Element

The extracellular matrix (ECM) is the non-cellular component of the tissues of our organism. It is the dynamic element that maintains a biochemical structure capable of supporting the organization and architecture of the tissue constituents. The diversity of ECM’s constituents gives it the biochemical and biophysical properties necessary to regulate its behavior and differentiation. ECM has an important role in the biology of cancer cell development and progression. Human papillomavirus infection (HPV) is the principal etiological agent of the most common sexually transmitted diseases. It is a virus that can cause lesions precursors of epithelial squamous and glandular tumors. Type 16 (HPV16) is the leading cause of pre-malignant lesions and invasive cancers in these tissues. This work will focus on HPV infection to understand the role of ECM in the invasion, spread, and pathogenesis of the lesions caused by this virus. Cancer is no longer considered a pathology explained only by uncontrolled proliferation and apoptosis but also by the deregulation of the microenvironment.

scholarly journals The Functional Role of Extracellular Matrix Proteins in Cancer

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 238
Author(s):  
Nadezhda V. Popova ◽  
Manfred Jücker
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Functional Role ◽  
Signaling Cascades ◽  
Surface Receptors ◽  
Current State ◽  
Composition And Structure ◽  
Major Structural Component

The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.

scholarly journals Versican: A Dynamic Regulator of the Extracellular Matrix

2020 ◽  
Vol 68 (11) ◽  
pp. 763-775
Author(s):  
Shamima Islam ◽  
Hideto Watanabe
Keyword(s):  
Extracellular Matrix ◽  
Dermatan Sulfate ◽  
Splice Variants ◽  
Repair Process ◽  
Dermatan Sulfate Proteoglycan ◽  
Cancer Aggressiveness ◽  
A Disintegrin And Metalloproteinase ◽  
A Site ◽  
The Brain

Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan belonging to the aggrecan/lectican family. In adults, this proteoglycan serves as a structural macromolecule of the extracellular matrix in the brain and large blood vessels. In contrast, versican is transiently expressed at high levels during development and under pathological conditions when the extracellular matrix dramatically changes, including in the inflammation and repair process. There are many reports showing the upregulation of versican in cancer, which correlates with cancer aggressiveness. Versican has four classical splice variants, and all the variants contain G1 and G3 domains at N- and C-termini, respectively. There are two glycosaminoglycan attachment domains CSα and CSβ. The largest V0 variant contains both CSα and CSβ, V1 contains CSβ, V2 contains CSα, and the shortest G3 variant has neither of them. Versican degradation is initiated by cleavage at a site in the CSβ domain by ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases. The N-terminal fragment containing the G1 domain has been reported to exert various biological functions, although its mechanisms of action have not yet been elucidated. In this review, we describe the role of versican in inflammation and cancer and also address the biological function of versikine.

scholarly journals Behavior of Metalloproteinases in Adipose Tissue, Liver and Arterial Wall: An Update of Extracellular Matrix Remodeling

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 158 ◽  
Author(s):  
Gabriela Berg ◽  
Magalí Barchuk ◽  
Verónica Miksztowicz
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Liver Fibrosis ◽  
Expression Patterns ◽  
Tissue Expansion ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Plaque Development ◽  
High Incidence

Extracellular matrix (ECM) remodeling is required for many physiological and pathological processes. Metalloproteinases (MMPs) are endopeptidases which are able to degrade different components of the ECM and nucleus matrix and to cleave numerous non-ECM proteins. Among pathological processes, MMPs are involved in adipose tissue expansion, liver fibrosis, and atherosclerotic plaque development and vulnerability. The expression and the activity of these enzymes are regulated by different hormones and growth factors, such as insulin, leptin, and adiponectin. The controversial results reported up to this moment regarding MMPs behavior in ECM biology could be consequence of the different expression patterns among species and the stage of the studied pathology. The aim of the present review was to update the knowledge of the role of MMPs and its inhibitors in ECM remodeling in high incidence pathologies such as obesity, liver fibrosis, and cardiovascular disease.

scholarly journals Heparanase: A Multitasking Protein Involved in Extracellular Matrix (ECM) Remodeling and Intracellular Events

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 236 ◽  
Author(s):  
Valentina Masola ◽  
Gloria Bellin ◽  
Giovanni Gambaro ◽  
Maurizio Onisto
Keyword(s):  
Extracellular Matrix ◽  
Enzymatic Activity ◽  
Current Knowledge ◽  
Transmembrane Proteins ◽  
Ecm Remodeling ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Low Levels ◽  
And Diffusion

Heparanase (HPSE) has been defined as a multitasking protein that exhibits a peculiar enzymatic activity towards HS chains but which simultaneously performs other non-enzymatic functions. Through its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thus contributing to the remodeling of the extracellular matrix and of the basal membranes. Furthermore, thanks to this activity, HPSE also promotes the release and diffusion of various HS-linked molecules like growth factors, cytokines and enzymes. In addition to being an enzyme, HPSE has been shown to possess the ability to trigger different signaling pathways by interacting with transmembrane proteins. In normal tissue and in physiological conditions, HPSE exhibits only low levels of expression restricted only to keratinocytes, trophoblast, platelets and mast cells and leukocytes. On the contrary, in pathological conditions, such as in tumor progression and metastasis, inflammation and fibrosis, it is overexpressed. With this brief review, we intend to provide an update on the current knowledge about the different role of HPSE protein exerted by its enzymatic and non-enzymatic activity.

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