scholarly journals Endogenously-Produced Hyaluronan and Its Potential to Regulate the Development of Peritoneal Adhesions

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 45
Author(s):  
Anna Kocurkova ◽  
Kristina Nesporova ◽  
Miriam Sandanusova ◽  
Michaela Kerberova ◽  
Katerina Lehka ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Abdominal Surgery ◽  
Glucuronic Acid ◽  
Abdominal Cavity ◽  
Peritoneal Membrane ◽  
Peritoneal Adhesions ◽  
Mesenchymal Transition ◽  
Sulfated Glycosaminoglycan ◽  
Fibrotic Tissue

Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs—mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This review considers the role of endogenously produced HA in the context of different fibrosis-related pathologies and its overlap in the development of PA.

scholarly journals Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer

2021 ◽  
Vol 22 (21) ◽  
pp. 11496
Author(s):  
Lucía Pascual-Antón ◽  
Beatriz Cardeñes ◽  
Ricardo Sainz de la Cuesta ◽  
Lucía González-Cortijo ◽  
Manuel López-Cabrera ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Metastasis ◽  
Abdominal Cavity ◽  
Mesothelial Cell ◽  
Metastatic Niche ◽  
Mesenchymal Transition ◽  
Disseminated Disease ◽  
Carcinoma Associated Fibroblasts ◽  
Peritoneal Mesothelial Cell

Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.

scholarly journals Role of extracellular matrix in breast cancer development: a brief update

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 274 ◽  
Author(s):  
Manoj Kumar Jena ◽  
Jagadeesh Janjanam
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Cancer Development ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Breast Cancer Development ◽  
Cancer Pathogenesis

Evidence is increasing on the crucial role of the extracellular matrix (ECM) in breast cancer progression, invasion and metastasis with almost all mortality cases owing to metastasis. The epithelial-mesenchymal transition is the first signal of metastasis involving different transcription factors such as Snail, TWIST, and ZEB1. ECM remodeling is a major event promoting cancer invasion and metastasis; where matrix metalloproteinases (MMPs) such as MMP-2, -9, -11, and -14 play vital roles degrading the matrix proteins for cancer spread. The β-D mannuronic acid (MMP inhibitor) has anti-metastatic properties through inhibition of MMP-2, and -9 and could be a potential therapeutic agent. Besides the MMPs, the enzymes such as LOXL2, LOXL4, procollagen lysyl hydroxylase-2, and heparanase also regulate breast cancer progression. The important ECM proteins like integrins (b1-, b5-, and b6- integrins), ECM1 protein, and Hic-5 protein are also actively involved in breast cancer development. The stromal cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and adipocytes also contribute in tumor development through different processes. The TAMs become proangiogenic through secretion of VEGF-A and building vessel network for nourishment and invasion of the tumor mass. The latest developments of ECM involvement in breast cancer progression has been discussed in this review and this study will help researchers in designing future work on breast cancer pathogenesis and developing therapy targeted to the ECM components.

Role of extracellular matrix in regulating embryonic epithelial-mesenchymal transition

2012 ◽  
Vol 3 (4) ◽  
pp. 333-344
Author(s):  
Francesca Zito
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Mesenchymal Transition ◽  
Membrane Receptors ◽  
Mesenchymal Transition ◽  
Functional Studies ◽  
Cell Matrix ◽  
Fibrotic Diseases ◽  
Cell Matrix Adhesion ◽  
Specific Membrane

AbstractEmbryogenesis and morphogenesis are characterized by complex cell rearrangements and movements which require appropriate interactions of cells with the surrounding extracellular matrix (ECM) by means of specific membrane receptors. Interest in the identification and purification of ECM components, as well as in conducting functional studies of them, including their ligands and other molecules involved in cell-matrix adhesion, has intensified in recent years, increasing our knowledge of developmental machinery. Cellular movements play an important role during the epithelial-mesenchymal transition (EMT) events, which are key processes in normal embryogenesis as well as in pathological conditions, such as fibrotic diseases and cancer. Thus, to more fully understand mechanisms underlying the EMT process, and for better knowledge of the embryonic defects related to this process, it would be useful to study the substrates on which EMT cells move during embryo development. This review focuses on a few different embryonic systems, taking into account the cell migration that occurs during EMT and highlighting, in particular, studies describing the direct involvement of ECM molecules.

scholarly journals Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response

2021 ◽  
Vol 8 ◽  
Author(s):  
Ana Catarina Silva ◽  
Cassilda Pereira ◽  
Ana Catarina R. G. Fonseca ◽  
Perpétua Pinto-do-Ó ◽  
Diana S. Nascimento
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Development ◽  
Cardiac Cells ◽  
Cellular Processes ◽  
Fibrotic Tissue ◽  
Short Period ◽  
And Function ◽  
Regenerative Therapies ◽  
The Impact

The extracellular matrix (ECM) is an essential component of the heart that imparts fundamental cellular processes during organ development and homeostasis. Most cardiovascular diseases involve severe remodeling of the ECM, culminating in the formation of fibrotic tissue that is deleterious to organ function. Treatment schemes effective at managing fibrosis and promoting physiological ECM repair are not yet in reach. Of note, the composition of the cardiac ECM changes significantly in a short period after birth, concurrent with the loss of the regenerative capacity of the heart. This highlights the importance of understanding ECM composition and function headed for the development of more efficient therapies. In this review, we explore the impact of ECM alterations, throughout heart ontogeny and disease, on cardiac cells and debate available approaches to deeper insights on cell–ECM interactions, toward the design of new regenerative therapies.

scholarly journals The extracellular matrix protein agrin is essential for epicardial epithelial-to-mesenchymal transition during heart development

2020 ◽  
Author(s):  
Xin Sun ◽  
Sophia Malandraki-Miller ◽  
Tahnee Kennedy ◽  
Elad Bassat ◽  
Konstantinos Klaourakis ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Golgi Apparatus ◽  
Basement Membrane ◽  
Heart Development ◽  
Focal Adhesions ◽  
Embryonic Heart ◽  
Extracellular Matrix Protein ◽  
Mesenchymal Transition ◽  
Epicardial Cells

AbstractDuring embryonic heart development, epicardial cells residing within the outer layer of the heart undergo epithelial-mesenchymal transition (EMT) and migrate into the myocardium to support and stimulate organ growth and morphogenesis. Disruption of epicardial EMT results in aberrant heart formation and embryonic lethality. Despite being an essential process during development, the regulation of epicardial EMT is poorly understood. Here we report EMT on the epicardial surface of the embryonic heart at subcellular resolution using scanning electron microscopy (SEM). We identified high- and low-EMT regions within the mesothelial layer of the epicardium and an association with key components of the extracellular matrix (ECM). The ECM basement membrane-associated proteoglycan agrin was found to localize in the epicardium in regions actively undergoing EMT. Deletion of agrin resulted in impaired EMT and compromised development of the epicardium, accompanied by down-regulation of the epicardial EMT regulator WT1. Agrin enhanced EMT in human embryonic stem cell-derived epicardial-like cells by decreasing β-catenin and promoting pFAK localization at focal adhesions. In addition, agrin promoted the aggregation of its receptor dystroglycan to the Golgi apparatus in murine epicardial cells and loss of agrin resulted in dispersal of dystroglycan throughout the epicardial cells in embryos, disrupting basement membrane integrity and impairing EMT. Our results provide new insights into the role of the ECM in heart development, and implicate agrin as a critical regulator of EMT, functioning to ensure dystroglycan connects signals between the ECM and activated epicardial cells.Summary statementThe basement membrane-associated proteoglycan agrin regulates epicardial epithelia-to-mesenchyme transition (EMT) through dystroglycan localizing on the Golgi apparatus. This ensures ECM and cytoskeletal connectivity and mechanical integrity of the transitioning epicardium and has important implications for the role of the extracellular matrix (ECM) in heart development.

scholarly journals Role of extracellular matrix in breast cancer development: a brief update

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 274 ◽  
Author(s):  
Manoj Kumar Jena ◽  
Jagadeesh Janjanam
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Cancer Development ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Breast Cancer Development ◽  
Cancer Pathogenesis

Evidence is increasing on the crucial role of the extracellular matrix (ECM) in breast cancer progression, invasion and metastasis with almost all mortality cases owing to metastasis. The epithelial-mesenchymal transition is the first signal of metastasis involving different transcription factors such as Snail, TWIST, and ZEB1. ECM remodeling is a major event promoting cancer invasion and metastasis; where matrix metalloproteinases (MMPs) such as MMP-2, -9, -11, and -14 play vital roles degrading the matrix proteins for cancer spread. The β-D mannuronic acid (MMP inhibitor) has anti-metastatic properties through inhibition of MMP-2, and -9 and could be a potential therapeutic agent. Besides the MMPs, the enzymes such as LOXL2, LOXL4, procollagen lysyl hydroxylase-2, and heparanase also regulate breast cancer progression. The important ECM proteins like integrins (b1-, b5-, and b6- integrins), ECM1 protein, and Hic-5 protein are also actively involved in breast cancer development. The stromal cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and adipocytes also contribute in tumor development through different processes. The TAMs become proangiogenic through secretion of VEGF-A and building vessel network for nourishment and invasion of the tumor mass. The latest developments of ECM involvement in breast cancer progression has been discussed in this review and this study will help researchers in designing future work on breast cancer pathogenesis and developing therapy targeted to the ECM components.

TMEM88 inhibits TGF-β1-induced-extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) program in human pleural mesothelial cells through modulating TGF-β1/Smad pathway

2020 ◽  
Author(s):  
Zhongmin Sun ◽  
Ning Qian ◽  
Hong Li ◽  
Tinghua Hu ◽  
Ling Tang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Mesenchymal Transition ◽  
Mesothelial Cell ◽  
Pathological Process ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Pleural Fibrosis ◽  
Tgf Β1

Abstract Pleural fibrosis is an irreversible pathological process occurred in the development of several lung diseases. TMEM88 is a member of transmembrane (TMEM) family and has been found to be involved in the regulation of fibrogenesis. However, the role of TMEM88 in pleural fibrosis remains unknown. In this study, we aimed to explore the role of TMEM88 in pleural fibrosis in vitro using TGF-β1-induced human pleural mesothelial cell line MeT-5A cells. Our results showed that the expression levels of TMEM88 were downregulated in pleural fibrosis tissues and TGF-β1-treated Met-5A cells. Overexpression of TMEM88 inhibited the proliferation of Met-5A cells under TGF-β1 stimulation. In addition, TMEM88 overexpression prevented TGF-β1-induced extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) in Met-5A cells with decreased expression levels of Col I and fibronectin, increased levels of cytokeratin-8 and E-cadherin, as well as decreased levels of vimentin and α-SMA. Furthermore, overexpression of TMEM88 inhibited the expression of TGF-β receptor I (TβRI) and TβRII and suppressed the phosphorylation of Smad2 and Smad3 in Met-5A cells. In conclusion, these results indicated that TMEM88 exhibited an anti-fibrotic activity in pleural fibrosis via inhibiting the activation of TGF-β1/Smad signaling pathway.

scholarly journals Role of the extracellular matrix in cancer-associated epithelial to mesenchymal transition phenomenon

2017 ◽  
Vol 247 (3) ◽  
pp. 368-381 ◽  
Author(s):  
George Tzanakakis ◽  
Rafaela-Maria Kavasi ◽  
Kallirroi Voudouri ◽  
Aikaterini Berdiaki ◽  
Ioanna Spyridaki ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Transition Phenomenon

scholarly journals Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 713
Author(s):  
Vasiliki Zolota ◽  
Vasiliki Tzelepi ◽  
Zoi Piperigkou ◽  
Helen Kourea ◽  
Efthymia Papakonstantinou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Critical Role ◽  
Epigenetic Alterations ◽  
Mesenchymal Transition ◽  
3D Network

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer characterized by genomic complexity and therapeutic options limited to only standard chemotherapy. Although it has been suggested that stratifying TNBC patients by pathway-specific molecular alterations may predict benefit from specific therapeutic agents, application in routine clinical practice has not yet been established. There is a growing body of the literature supporting that epigenetic modifications comprised by DNA methylation, chromatin remodeling and non-coding RNAs play a fundamental role in TNBC pathogenesis. Extracellular matrix (ECM) is a highly dynamic 3D network of macromolecules with structural and cellular regulatory roles. Alterations in the expression of ECM components result in uncontrolled matrix remodeling, thus affecting its ability to regulate vital functions of cancer cells, including proliferation, migration, adhesion, invasion and epithelial-to-mesenchymal transition (EMT). Recent molecular data highlight the major role of tumor microenvironment and ECM alterations in TNBC and approaches for targeting tumor microenvironment have recently been recognized as potential therapeutic strategies. Notably, many of the ECM/EMT modifications in cancer are largely driven by epigenetic events, highlighting the pleiotropic effects of the epigenetic network in TNBC. This article presents and critically discusses the current knowledge on the epigenetic alterations correlated with TNBC pathogenesis, with emphasis on those associated with ECM/EMT modifications, their prognostic and predictive value and their use as therapeutic targets.

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