Abstract
The specific organization of the tumor extracellular matrix (ECM) is an intrinsic and basic step in the convoluted pathways of tumorigenesis. Fibrosarcoma is a rare, lethal, malignant tumor originating from fibroblasts, characterized by the formation of an abundant ECM. Fibroblastoid cells undergoing malignant transformation specifically alter composition and organization of their ECM to facilitate growth, survival and invasion. Fibrosarcoma cells were shown to have a high content and turnover of ECM components including hyaluronan, proteoglycans, collagens, fibronectin and laminin. Cell signaling by endogenous growth factors, such as TGFβ, EGF, FGF2, VEGF and IFG-I, is directly correlated to ECM remodeling, stroma formation and fibrosarcoma progression. In this regard, growth factors affect the expression of matrix macromolecules, such as secreted and cell-associated proteoglycans, hyaluronan and its receptors CD44 and RHAMM, as well as the expression and activity of matrix- degrading metalloproteinases, which are of critical importance in tissue remodeling and fibrosarcoma progression. Therefore, therapeutic approaches considering growth factors and their receptors as well as downstream signaling in human cancers may well be pharmacological targets being currently explored. In this article, we focus on growth factor signaling regulating fibrosarcoma cell ECM organization at the level of deposition and degradation of ECM macromolecules, the relation of ECM remodeling with fibrosarcoma cell malignant behaviour as well as the putative strategies for its therapeutic intervention.
Keywords: Fibrosarcoma, extracellular matrix, growth factors, therapeutic targets, tumor cell signalling.
Current Medicinal Chemistry
Title:Could Growth Factor-Mediated Extracellular Matrix Deposition and Degradation Offer the Ground for Directed Pharmacological Targeting in Fibrosarcoma?
Volume: 20 Issue: 23
Author(s): D. Nikitovic, A. Berdiaki, A. Banos, A. Tsatsakis, N. K. Karamanos and G. N. Tzanakakis
Affiliation:
Keywords: Fibrosarcoma, extracellular matrix, growth factors, therapeutic targets, tumor cell signalling.
Abstract: The specific organization of the tumor extracellular matrix (ECM) is an intrinsic and basic step in the convoluted pathways of tumorigenesis. Fibrosarcoma is a rare, lethal, malignant tumor originating from fibroblasts, characterized by the formation of an abundant ECM. Fibroblastoid cells undergoing malignant transformation specifically alter composition and organization of their ECM to facilitate growth, survival and invasion. Fibrosarcoma cells were shown to have a high content and turnover of ECM components including hyaluronan, proteoglycans, collagens, fibronectin and laminin. Cell signaling by endogenous growth factors, such as TGFβ, EGF, FGF2, VEGF and IFG-I, is directly correlated to ECM remodeling, stroma formation and fibrosarcoma progression. In this regard, growth factors affect the expression of matrix macromolecules, such as secreted and cell-associated proteoglycans, hyaluronan and its receptors CD44 and RHAMM, as well as the expression and activity of matrix- degrading metalloproteinases, which are of critical importance in tissue remodeling and fibrosarcoma progression. Therefore, therapeutic approaches considering growth factors and their receptors as well as downstream signaling in human cancers may well be pharmacological targets being currently explored. In this article, we focus on growth factor signaling regulating fibrosarcoma cell ECM organization at the level of deposition and degradation of ECM macromolecules, the relation of ECM remodeling with fibrosarcoma cell malignant behaviour as well as the putative strategies for its therapeutic intervention.
Export Options
About this article
Cite this article as:
Nikitovic D., Berdiaki A., Banos A., Tsatsakis A., Karamanos K. N. and Tzanakakis N. G., Could Growth Factor-Mediated Extracellular Matrix Deposition and Degradation Offer the Ground for Directed Pharmacological Targeting in Fibrosarcoma?, Current Medicinal Chemistry 2013; 20 (23) . https://dx.doi.org/10.2174/0929867311320230003
DOI https://dx.doi.org/10.2174/0929867311320230003 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
In Search of Natural Remediation for Cervical Cancer
Anti-Cancer Agents in Medicinal Chemistry Past, Present and Future Therapeutics for Cerebellar Ataxias
Current Neuropharmacology Emerging Role of the Ubiquitin-proteasome System as Drug Targets
Current Pharmaceutical Design Prevention of Microbial Communities: Novel Approaches Based Natural Products
Current Pharmaceutical Biotechnology Therapeutic Applications of Curcumin and its Novel Formulations in the Treatment of Bladder Cancer: A Review of Current Evidence
Anti-Cancer Agents in Medicinal Chemistry The Applications of Targeting Anti-Cancer Agents in Cancer Therapeutics
Anti-Cancer Agents in Medicinal Chemistry Novel Approaches Towards Designing of Isoform-Selective Inhibitors Against Class II Histone Deacetylases: The Acute Requirement for Targetted Anticancer Therapy
Current Topics in Medicinal Chemistry Molecular Mechanisms, Proteinopathies and Therapeutic Strategies in Neurodegenerative Disorders
Current Genomics Breaking the DNA Damage Response via Serine/Threonine Kinase Inhibitors to Improve Cancer Treatment
Current Medicinal Chemistry Synthesis and Antitumor Evaluation of Novel N-substituted Norcantharidin Imidazolium Derivatives
Current Organic Synthesis Incretin-Based Antidiabetic Agents for the Management of Non-Alcoholic Fatty Liver Disease
Current Vascular Pharmacology May Patients with Alcohol Liver Disease Benefit from Herbal Medicines?
Reviews on Recent Clinical Trials A Review of Surgical Options to Preserve Fertility in the Treatment of Early Cervical Cancer
Current Women`s Health Reviews FTY720: A Most Promising Immunosuppressant Modulating Immune Cell Functions
Mini-Reviews in Medicinal Chemistry Impact of Renin-Angiotensin System in Hepatocellular Carcinoma
Current Cancer Drug Targets Synthesis, In Vitro Activities of (2-Cyclopropoxyphenyl)piperidine Derivatives for α1a and α1d Adrenergic Receptor Inhibitors
Medicinal Chemistry Ketamine as Antidepressant? Current State and Future Perspectives
Current Neuropharmacology DNA Topoisomerase II Enzymes as Molecular Targets for Cancer Chemotherapy
Current Cancer Drug Targets The Role of the Metabolism of Anticancer Drugs in Their Induced-Cardiotoxicity
Current Drug Metabolism Current Status and Future Perspectives of Chemoprevention in Head and Neck Cancer
Current Cancer Drug Targets