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
-
DNA Methylation and Bladder Cancer: Where Genotype does not Predict Phenotype
Current Genomics Recent Approaches in Chemoprevention of Prostate Cancer
Current Cancer Drug Targets Angiogenesis Inhibitors: Implications for Combination with Conventional Therapies
Current Pharmaceutical Design Quantitative Structure-Wavelength Relationship Modeling of Porphin -Derivative Photosensitizers
Combinatorial Chemistry & High Throughput Screening Analysis of the Potential for HIV-1 Vpr as an Anti-Cancer Agent
Current HIV Research Tetrapyrrolic Macrocycles: Potentialities in Medical Imaging Technologies
Current Organic Synthesis Principles of an Adenovirus-Based Assay for Candidate Compounds with Broad Spectrum of Anti-Neoplastic Activities
Letters in Drug Design & Discovery α-Lipoic Acid Supplementation: A Tool for Obesity Therapy?
Current Pharmaceutical Design Differentiation-Inducing Therapy for Solid Tumors
Current Pharmaceutical Design Transient Receptor Potential Vanilloid 1 Channel Modulation: A Novel Approach to Pain Therapy
Current Bioactive Compounds Intracellular Trafficking of MDR Transporters and Relevance of SNPs
Current Topics in Medicinal Chemistry Bioprospecting for Functionally-Proficient Potential Probiotics
Current Nutrition & Food Science Subject Index To Volume 6
Current Topics in Medicinal Chemistry Heparin - a Key Drug in the Treatment of the Circulatory Degenerative Diseases: Controlling its Action with Polymers
Current Pharmaceutical Design Pharmacological Effect of Berberine Chloride in Propyl Thiouracil Induced Thyroidal Dysfunction - A Time Bound Study in Female Rats
Recent Patents on Drug Delivery & Formulation Role of Polysaccharides Mimetic Components in Targeted Cancer Treatment
Current Drug Targets Validated RP-HPLC Method for the Simultaneous Analysis of Gemcitabine and LY-364947 in Liposomal Formulations
Current Drug Targets Potential Role of Rho Kinase Inhibitors in Combating Diabetes-Related Complications Including Diabetic Neuropathy-A Review
Current Diabetes Reviews Efficacy and Safety of the Combination of Docetaxel (Taxotere®) with Targeted Therapies in the Treatment of Solid Malignancies
Current Drug Targets MiR-509-3-5p-NONHSAT112228.2 Axis Regulates p21 and Suppresses Proliferation and Migration of Lung Cancer Cells
Current Topics in Medicinal Chemistry