Contribution of the Extracellular Matrix to Growth Properties of Cells from a Preneoplastic Outgrowth: Possible Role of Hyaluronic Acid

Pathobiology ◽  
1987 ◽  
Vol 55 (6) ◽  
pp. 313-321 ◽  
Author(s):  
Catherine A. Elstad ◽  
Howard L. Hosick
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Growth Properties

scholarly journals Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens

2019 ◽  
Author(s):  
Sara Pedron ◽  
Gabrielle L. Wolter ◽  
Jee-Wei E. Chen ◽  
Sarah E. Laken ◽  
Jann N. Sarkaria ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Tumor Microenvironment ◽  
Kinase Inhibitor ◽  
Egfr Mutations ◽  
Primary Glioblastoma ◽  
Stat3 Phosphorylation

AbstractTherapeutic options to treat primary glioblastoma (GBM) tumors are scarce. GBM tumors with epidermal growth factor receptor (EGFR) mutations, in particular a constitutively active EGFRvIII mutant, have extremely poor clinical outcomes. GBM tumors with concurrent EGFR amplification and active phosphatase and tensin homolog (PTEN) are sensitive to the tyrosine kinase inhibitor erlotinib, but the effect is not durable. A persistent challenge to improved treatment is the poorly understood role of cellular, metabolic, and biophysical signals from the GBM tumor microenvironment on therapeutic efficacy and acquired resistance. The intractable nature of studying GBM cell in vivo motivates tissue engineering approaches to replicate aspects of the complex GBM tumor microenvironment. Here, we profile the effect of erlotinib on two patient-derived GBM specimens: EGFR+ GBM12 and EGFRvIII GBM6. We use a three-dimensional gelatin hydrogel to present brain-mimetic hyaluronic acid (HA) and evaluate the coordinated influence of extracellular matrix signals and EGFR mutation status on GBM cell migration, survival and proliferation, as well as signaling pathway activation in response to cyclic erlotinib exposure. Comparable to results observed in vivo for xenograft tumors, erlotinib exposure is not cytotoxic for GBM6 EGFRvIII specimens. We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBM EGFR+ cells by modifying STAT3 phosphorylation status. Taken together, we report an in vitro tissue engineered platform to monitor signaling associated with poor response to targeted inhibitors in GBM.

The crosstalk of hyaluronan-based extracellular matrix and synapses

2008 ◽  
Vol 4 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Renato Frischknecht ◽  
Constanze I. Seidenbecher
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Hyaluronic Acid ◽  
Chondroitin Sulphate ◽  
Specific Form ◽  
Perineuronal Net ◽  
Chondroitin Sulphate Proteoglycans ◽  
And Function ◽  
Brain Extracellular Space

Many neurons and their synapses are enwrapped in a brain-specific form of the extracellular matrix (ECM), the so-called perineuronal net (PNN). It forms late in the postnatal development around the time when synaptic contacts are stabilized. It is made of glycoproteins and proteoglycans of glial as well as neuronal origin. The major organizing polysaccharide of brain extracellular space is the polymeric carbohydrate hyaluronic acid (HA). It forms the backbone of a meshwork consisting of CNS proteoglycans such as the lectican family of chondroitin sulphate proteoglycans (CSPG). This family comprises four abundant components of brain ECM: aggrecan and versican as broadly expressed CSPGs and neurocan and brevican as nervous-system-specific family members. In this review, we intend to focus on the specific role of the HA-based ECM in synapse development and function.

Hyaluronic acid and Regenerative medicine: New insights into the stroke therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Maryam Shahi ◽  
Daruosh Mohammadnejad ◽  
Mohammad Karimipour ◽  
Seyed Hossein Rasta ◽  
Reza Rahbarghazi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Regenerative Medicine ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Stroke Therapy ◽  
Therapeutic Approaches ◽  
Normal Tissues ◽  
Inflammatory Processes

: Stroke is known as one of very important public health problems which are related to a societal burden and tremendous economic. It has been showed, there are few therapeutic approaches in the treatment of this disease. In this regard, present therapeutic platforms aim to obtain neuroprotection, reperfusion, and neurorecovery. Among these therapies, regenerative medicine-based therapies have been appeared as new ways in stroke therapy. Hyaluronic acid (HA) is a new candidate which could be applied as regerenative medicine-based therapy in the treatment of stroke. HA is a glycosaminoglycan which is formed of repeating disaccharide units (D-glucuronic acid and N-acetyl-D-glucosamine). Multiple lines evidence demonstrated that HA has critical roles in normal tissues. It can be key players in different physiological and pathophysiological conditions such as water homeostasis, multiple drug resistance, inflammatory processes, tumorigenesis, angiogenesis, and changed viscoelasticity of extracellular matrix. HA has very important physicochemical properties (i.e., availability of reactive functional groups and its solubility which makes it as a biocompatible material for applying in the regenerative medicine. Given that HA-based bioscaffolds and biomaterials do not induce inflammation or allergies and are hydrophilic which have introduced them as soft tissue fillers and injectable dermal. Several studies indicated that HA could be employed as new therapeutic candidate in the treatment of stroke. These studies documented that HA and HA-based therapies exert their pharmacology effects via affecting on stroke-related processes. Herein, we have summarized the role of extracellular matrix in stroke pathogenesis. Moreover, we highlighted the HA-based therapies in the treatment of stroke.

The role of extracellular matrix in the formation of the sclerotome

Development ◽  
1979 ◽  
Vol 54 (1) ◽  
pp. 75-98
Author(s):  
Michael Solursh ◽  
Marilyn Fisher ◽  
Stephen Meier ◽  
Carl T. Singley
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Cetylpyridinium Chloride ◽  
Cell Contact ◽  
Intercellular Spaces ◽  
In Ovo ◽  
Junctional Complexes ◽  
Apical Junctions ◽  
Scanning Electron

The development of the sclerotome is considered as a model for the formation of mesenchyme from an epithelium. In early epithelial somites, transmission and scanning electron microscopy indicate considerable ultrastructural similarity between the future sclerotome and dermamyotomal regions. Subsequently, these two regions diverge in their development. In the forming dermamyotome, junctional complexes become more extensive and the cells become elongated, closely applied to each other, and have angular surface contours. In the forming sclerotome, there is an early reduction in apical junctions. The cells elongate, keeping their original polarity, and acquire numerous filopodia which contain punctate junctions at sites of cell-to-cell contact. Associated with cellular extension is an expansion of the intercellular spaces which do not contain any ultrastructurally recognizable material. Evidence for a role of hyaluronic acid in the expansion of the intercellular spaces is presented. As identified by the susceptibility of cetylpyridinium chloride precipitates to Streptomyces hyaluronidase and chromatographic separation of chondroitinase ABC digestion products, as much as 64–68% of the [3H]glucosamine-labeled glycosaminoglycans synthesized by explanted somites is hyaluronic acid. In addition, hyaluronidase-sensitive label is localized in the intercellular spaces of the sclerotome, as demonstrated by autoradiography. When ,Streptomyces hyaluronidase is injected in ovo into living embryos, the sclerotomal mesenchyme differentiates morphologically, but intercellular spaces are drastically reduced. It is hypothesized that the sclerotomal cells produce a hyaluronate-enriched extracellular matrix which is inflated by hydration to mediate the expansion of the sclerotomal mass towards the notochord.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Translation ◽  
Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

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