scholarly journals Extracellular Matrix Influencing HGF/c-MET Signaling Pathway: Impact on Cancer Progression

2018 ◽  
Vol 19 (11) ◽  
pp. 3300 ◽  
Author(s):  
Heydi Noriega-Guerra ◽  
Vanessa Freitas
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Cell Communication ◽  
Dynamic Network ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Matricellular Proteins ◽  
Cellular Processes

The extracellular matrix (ECM) is a crucial component of the tumor microenvironment involved in numerous cellular processes that contribute to cancer progression. It is acknowledged that tumor–stromal cell communication is driven by a complex and dynamic network of cytokines, growth factors and proteases. Thus, the ECM works as a reservoir for bioactive molecules that modulate tumor cell behavior. The hepatocyte growth factor (HGF) produced by tumor and stromal cells acts as a multifunctional cytokine and activates the c-MET receptor, which is expressed in different tumor cell types. The HGF/c-MET signaling pathway is associated with several cellular processes, such as proliferation, survival, motility, angiogenesis, invasion and metastasis. Moreover, c-MET activation can be promoted by several ECM components, including proteoglycans and glycoproteins that act as bridging molecules and/or signal co-receptors. In contrast, c-MET activation can be inhibited by proteoglycans, matricellular proteins and/or proteases that bind and sequester HGF away from the cell surface. Therefore, understanding the effects of ECM components on HGF and c-MET may provide opportunities for novel therapeutic strategies. Here, we give a short overview of how certain ECM components regulate the distribution and activation of HGF and c-MET.

scholarly journals Precancerous niche (PCN), a product of fibrosis with remodeling by incessant chronic inflammation

4open ◽  
2019 ◽  
Vol 2 ◽  
pp. 11 ◽  
Author(s):  
Björn L.D.M. Brücher ◽  
Ijaz S. Jamall
Keyword(s):  
Extracellular Matrix ◽  
Chronic Inflammation ◽  
Genetic Material ◽  
Cell Communication ◽  
Cell Types ◽  
Complex Signaling ◽  
Different Cell Types ◽  
Multiple Signaling ◽  
Extracellular Environment

Fibroblasts are actively involved in the creation of the stroma and the extracellular matrix which are important for cell adhesion, cell–cell communication, and tissue metabolism. The role of fibrosis in carcinogenesis can be examined by analogy to tissues of various cancers. The orchestration of letters in the interplay of manifold components with signaling and crosstalk is incompletely understood but available evidence suggests a hitherto underappreciated role for fibrosis in carcinogenesis. Complex signaling and crosstalk by pathogenic stimuli evoke persistent subclinical inflammation, which in turn, results in a cascade of different cell types, ubiquitous proteins and their corresponding enzymes, cytokine releases, and multiple signaling pathways promoting the onset of fibrosis. There is considerable evidence that the body's attempt to resolve such a modified extracellular environment leads to further disruption of homeostasis and the genesis of the precancerous niche as part of the six-step process that describes carcinogenesis. The precancerous niche is formed and can be understood to develop as a result of (1) pathogenic stimulus, (2) chronic inflammation, and (3) fibrosis with alterations of the extracellular matrix, stromal rigidity, and mechano-transduction. This is why carcinogenesis is not just a process of aberrant cell growth with damaged genetic material but the role of the PCN in its entirety reveals how carcinogenesis can occur without invoking the need for somatic mutations.

scholarly journals Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 817 ◽  
Author(s):  
Alejandra Hernández ◽  
Juan Pablo Arab ◽  
Daniela Reyes ◽  
Ainhoa Lapitz ◽  
Han Moshage ◽  
...  
Keyword(s):  
Liver Disease ◽  
Extracellular Vesicles ◽  
Liver Diseases ◽  
Experimental Studies ◽  
Cell Communication ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Therapeutic Implications ◽  
Isolation And Characterization ◽  
Liver Disease Progression

In recent years, knowledge on the biology and pathobiology of extracellular vesicles (EVs) has exploded. EVs are submicron membrane-bound structures secreted from different cell types containing a wide variety of bioactive molecules (e.g., proteins, lipids, and nucleic acids (coding and non-coding RNA) and mitochondrial DNA). EVs have important functions in cell-to-cell communication and are found in a wide variety of tissues and body fluids. Better delineation of EV structures and advances in the isolation and characterization of their cargo have allowed the diagnostic and therapeutic implications of these particles to be explored. In the field of liver diseases, EVs are emerging as key players in the pathogenesis of both nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD), the most prevalent liver diseases worldwide, and their complications, including development of hepatocellular carcinoma. In these diseases, stressed/damaged hepatocytes release large quantities of EVs that contribute to the occurrence of inflammation, fibrogenesis, and angiogenesis, which are key pathobiological processes in liver disease progression. Moreover, the specific molecular signatures of released EVs in biofluids have allowed EVs to be considered as promising candidates to serve as disease biomarkers. Additionally, different experimental studies have shown that EVs may have potential for therapeutic use as a liver-specific delivery method of different agents, taking advantage of their hepatocellular uptake through interactions with specific receptors. In this review, we focused on the most recent findings concerning the role of EVs as new structures mediating autocrine and paracrine intercellular communication in both ALD and NAFLD, as well as their potential use as biomarkers of disease severity and progression. Emerging therapeutic applications of EVs in these liver diseases were also examined, along with the potential for successful transition from bench to clinic.

MP41-03 NOTCH SIGNALING PATHWAY AS COMMON TARGET OF ERG IN DIVERSE TUMOR CELL TYPES

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Ahmed Mohamed ◽  
Lakshmi Ravindranath ◽  
Shilpa Katta ◽  
Shyh-Han Tan ◽  
Yongmei Chen ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Common Target

scholarly journals Cytonemes in Tumourigenesis

2019 ◽  
Author(s):  
Marta Portela
Keyword(s):  
Cancer Progression ◽  
Tumour Progression ◽  
Cell Signalling ◽  
Cell Communication ◽  
Cell Types ◽  
Wing Disc ◽  
Genetic Ablation ◽  
The Past ◽  
Tumoral Cell ◽  
To Receive

Increasing evidence during the past two decades shows that cells interconnect and communicate through cytonemes. These cytoskeleton-driven extensions of specialized membrane territories have emerged as a novel alternative for cell to cell communication that are involved in development, physiology, and disease. Several recent studies have shown that signalling pathways mediated by cytonemes during development, are essential for certain tumoral cell types progression. In Drosophila wing disc EGFR and RET tumour models, cytoneme formation is required to receive signals from the neighbouring cells. Genetic ablation of cytonemes prevents tumour progression, restores apico-basal polarity, and improves survival. Furthermore, cytonemes in the Drosophila glial cells are essential for glioblastoma progression as they alter Wg/Fz1 signalling between glia and neurons. Research on cytoneme formation, maintenance, and cell signalling mechanisms will help to better understand not only physiological developmental processes and tissue homeostasis but also cancer progression.

scholarly journals Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy

2021 ◽  
Author(s):  
Christina J. Codden ◽  
Michael T. Chin
Keyword(s):  
Extracellular Matrix ◽  
Hypertrophic Cardiomyopathy ◽  
Dendritic Cell ◽  
Differentially Expressed Genes ◽  
Intercellular Communication ◽  
Cell Communication ◽  
Cell Types ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Differentially Expressed

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.

scholarly journals Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons

2022 ◽  
Vol 9 ◽  
Author(s):  
Maria Veronica Lipreri ◽  
Nicola Baldini ◽  
Gabriela Graziani ◽  
Sofia Avnet
Keyword(s):  
Extracellular Matrix ◽  
Bone Structure ◽  
Dynamic Network ◽  
Cell Types ◽  
New Drugs ◽  
Culture Methods ◽  
Increased Risk ◽  
Multiple Cell

As life expectancy increases, the population experiences progressive ageing. Ageing, in turn, is connected to an increase in bone-related diseases (i.e., osteoporosis and increased risk of fractures). Hence, the search for new approaches to study the occurrence of bone-related diseases and to develop new drugs for their prevention and treatment becomes more pressing. However, to date, a reliable in vitro model that can fully recapitulate the characteristics of bone tissue, either in physiological or altered conditions, is not available. Indeed, current methods for modelling normal and pathological bone are poor predictors of treatment outcomes in humans, as they fail to mimic the in vivo cellular microenvironment and tissue complexity. Bone, in fact, is a dynamic network including differently specialized cells and the extracellular matrix, constantly subjected to external and internal stimuli. To this regard, perfused vascularized models are a novel field of investigation that can offer a new technological approach to overcome the limitations of traditional cell culture methods. It allows the combination of perfusion, mechanical and biochemical stimuli, biological cues, biomaterials (mimicking the extracellular matrix of bone), and multiple cell types. This review will discuss macro, milli, and microscale perfused devices designed to model bone structure and microenvironment, focusing on the role of perfusion and encompassing different degrees of complexity. These devices are a very first, though promising, step for the development of 3D in vitro platforms for preclinical screening of novel anabolic or anti-catabolic therapeutic approaches to improve bone health.

scholarly journals P11.65 Insights into the mechanisms of primary brain tumor invasion

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii58-iii59
Author(s):  
A Bikfalvi ◽  
T Daubon ◽  
C Billottet
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Conformational Changes ◽  
Cell Invasion ◽  
Immune Cell ◽  
Tumor Cell Invasion ◽  
Migration And Invasion ◽  
Matricellular Proteins

Abstract We have made progress in unravelling the mechanisms of tumor cell invasion by focusing the attention on two molecular pathways including chemokines and extracellular matrix molecules. Chemokines are important mediators of cell signaling that operate both on normal cells and tumor cells and in the immune-cell compartment (Billottet et al, 2013). Among the chemokine receptors, CXCR3 mediate diverse biological functions and comes in two major isoforms the A and B isoform. We found that ligand affinities and conformational changes are very different for the A and B form. We have recently elucidated the role and mechanism of CXCR3A in GBM invasion (Boyé et al, 2017b). We demonstrated that agonist stimulation enhances in vitro cell migration and invasion in GBM cells. A major finding was that CXCR3A forms a complex with the trafficking receptor Lipoprotein-related receptor-1 (LRP1). Silencing of LRP1 leads to an increase in the magnitude of ligand-induced conformational change with CXCR3-A focalized at the cell membrane, leading to sustained receptor activity and increase in the migration. This was also clinically validated. Our study defines LRP1 as a new regulator of CXCR3 and indicates that targeting CXCR3-A in GBM may constitute a promising strategy to halt tumor cell invasion. The extracellular matrix (ECM) has morphogenic roles in tumors. Important ECM components are the matricellular proteins, called thrombospondins(THBS1-5) (Adams and Lawler 2011). We recently elucidated the complex role of THSB1 in GBM invasion (Daubon et al.2019). Global expression analysis revealed that THBS1 is up-regulated in GBMs and associated with a poor prognosis. We, furthermore, demonstrated that THBS1 did not activate TGFβ in GBM but that TGFβ1 induced the expression of THBS1 via SMAD3. Furthermore, GBM invasion is compromised when THBS1 is silenced in tumor cells. Thus, our data clearly show that THBS1 is not only involved in the regulation of angiogenesis in GBM, but also impacts the invasive behaviour of glioma cells by interacting with a molecule called CD47 expressed on the surface of GBM cells. RNA-sequencing after microdissection of central and peripheral tumour areas in a human PDX model demonstrated that THBS1 was the gene with the highest connectivity in the peripheral invasive tumour areas. Taken together, these data indicate that THBS1 plays important role in the infiltrative process in GBM. REFERENCES: Adams JC, Lawler J. Cold Spring Harb Perspect Biol. 2011;3:a009712 Billottet C, Quemener C, Bikfalvi A. Biochim Biophys Acta. 2013;1836:287- Boyé K et al. Sci Rep. 2017;7:10703 Boyé K et al. Nat Commun. 2017;8:1571 Daubon T et al, Nature Communications. Nat Commun. 2019 Mar 8;10(1):1146 Murphy-Ullrich JE, Poczatek M. Cytokine Growth Factor Rev. 2000 11:59

scholarly journals Ceramide Metabolism Balance, a Multifaceted Factor in Critical Steps of Breast Cancer Development

2018 ◽  
Vol 19 (9) ◽  
pp. 2527 ◽  
Author(s):  
Victor García-González ◽  
José Díaz-Villanueva ◽  
Octavio Galindo-Hernández ◽  
Israel Martínez-Navarro ◽  
Gustavo Hurtado-Ureta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Chemotherapy Resistance ◽  
Cell Communication ◽  
Low Grade ◽  
Cancer Disease ◽  
Cellular Processes ◽  
Neoplastic Processes ◽  
Key Factor ◽  
Inflammatory State

Ceramides are key lipids in energetic-metabolic pathways and signaling cascades, modulating critical physiological functions in cells. While synthesis of ceramides is performed in endoplasmic reticulum (ER), which is altered under overnutrition conditions, proteins associated with ceramide metabolism are located on membrane arrangement of mitochondria and ER (MAMs). However, ceramide accumulation in meta-inflammation, condition that associates obesity with a chronic low-grade inflammatory state, favors the deregulation of pathways such as insulin signaling, and induces structural rearrangements on mitochondrial membrane, modifying its permeability and altering the flux of ions and other molecules. Considering the wide biological processes in which sphingolipids are implicated, they have been associated with diseases that present abnormalities in their energetic metabolism, such as breast cancer. In this sense, sphingolipids could modulate various cell features, such as growth, proliferation, survival, senescence, and apoptosis in cancer progression; moreover, ceramide metabolism is associated to chemotherapy resistance, and regulation of metastasis. Cell–cell communication mediated by exosomes and lipoproteins has become relevant in the transport of several sphingolipids. Therefore, in this work we performed a comprehensive analysis of the state of the art about the multifaceted roles of ceramides, specifically the deregulation of ceramide metabolism pathways, being a key factor that could modulate neoplastic processes development. Under specific conditions, sphingolipids perform important functions in several cellular processes, and depending on the preponderant species and cellular and/or tissue status can inhibit or promote the development of metabolic and potentially breast cancer disease.

scholarly journals Dropping in on lipid droplets: insights into cellular stress and cancer

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Peter Shyu ◽  
Xing Fah Alex Wong ◽  
Karen Crasta ◽  
Guillaume Thibault
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Lipid Droplets ◽  
Cellular Stress ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Major Topic ◽  
Cellular Processes ◽  
Storage Studies ◽  
Cytoplasmic Structures

Lipid droplets (LD) have increasingly become a major topic of research in recent years following its establishment as a highly dynamic organelle. Contrary to the initial view of LDs being passive cytoplasmic structures for lipid storage, studies have provided support on how they act in concert with different organelles to exert functions in various cellular processes. Although lipid dysregulation resulting from aberrant LD homeostasis has been well characterised, how this translates and contributes to cancer progression is poorly understood. This review summarises the different paradigms on how LDs function in the regulation of cellular stress as a contributing factor to cancer progression. Mechanisms employed by a broad range of cancer cell types in differentially utilising LDs for tumourigenesis will also be highlighted. Finally, we discuss the potential of targeting LDs in the context of cancer therapeutics.

scholarly journals Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis

2021 ◽  
Vol 22 (9) ◽  
pp. 4340
Author(s):  
Iona J. MacDonald ◽  
Chien-Chung Huang ◽  
Shan-Chi Liu ◽  
Yen-You Lin ◽  
Chih-Hsin Tang
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Evidence Base ◽  
Ccn Proteins ◽  
Matricellular Proteins ◽  
Substantial Evidence ◽  
Ccn Family ◽  
Cellular Processes

The CCN family of matricellular proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.

Sign in / Sign up

Export Citation Format

Share Document