Abstract
The urokinase-type plasminogen activator receptor (uPAR) and its structural homologue C4.4A are multidomain members of the Ly6/uPAR/α-neurotoxin protein domain family. Both are glycosylphosphatidylinositol-anchored membrane glycoproteins encoded by neighbouring genes located on chromosome 19q13 in the human genome. The structural relationship between the two proteins is, however, not reflected at the functional level. Whereas uPAR has a wellestablished role in regulating and focalizing uPA-mediated plasminogen activation to the surface of those cells expressing the receptor, the biological function of C4.4A remains elusive. Nonetheless, both uPAR and C4.4A have been implicated in human pathologies such as wound healing and cancer. A large body of experimental evidence thus demonstrates that high levels of uPAR in resected tumour tissue as well as in plasma are associated with poor prognosis in a number of human cancers including colon adenocarcinoma and pulmonary squamous cell carcinoma. Targeting uPAR in experimental animal models has also provided promising results regarding the interference with pathogenic plasminogen activation. In the case of C4.4A, very recent data have demonstrated that high protein expression in tumour cells of non-small cell pulmonary adenocarcinomas is associated with a particularly severe disease progression. This review will evaluate structuralfunctional and disease-related aspects of uPAR and C4.4A with a view to possible pharmacological targeting strategies for therapy and for non-invasive bioimaging.
Keywords: uPAR, LU protein domain family, CD87, non-small cell lung cancer, prognosis, pharmacological targeting, peptide antagonists, PET
Current Medicinal Chemistry
Title: The Urokinase Receptor and its Structural Homologue C4.4A in Human Cancer: Expression, Prognosis and Pharmacological Inhibition
Volume: 15 Issue: 25
Author(s): B. Jacobsen and M. Ploug
Affiliation:
Keywords: uPAR, LU protein domain family, CD87, non-small cell lung cancer, prognosis, pharmacological targeting, peptide antagonists, PET
Abstract: The urokinase-type plasminogen activator receptor (uPAR) and its structural homologue C4.4A are multidomain members of the Ly6/uPAR/α-neurotoxin protein domain family. Both are glycosylphosphatidylinositol-anchored membrane glycoproteins encoded by neighbouring genes located on chromosome 19q13 in the human genome. The structural relationship between the two proteins is, however, not reflected at the functional level. Whereas uPAR has a wellestablished role in regulating and focalizing uPA-mediated plasminogen activation to the surface of those cells expressing the receptor, the biological function of C4.4A remains elusive. Nonetheless, both uPAR and C4.4A have been implicated in human pathologies such as wound healing and cancer. A large body of experimental evidence thus demonstrates that high levels of uPAR in resected tumour tissue as well as in plasma are associated with poor prognosis in a number of human cancers including colon adenocarcinoma and pulmonary squamous cell carcinoma. Targeting uPAR in experimental animal models has also provided promising results regarding the interference with pathogenic plasminogen activation. In the case of C4.4A, very recent data have demonstrated that high protein expression in tumour cells of non-small cell pulmonary adenocarcinomas is associated with a particularly severe disease progression. This review will evaluate structuralfunctional and disease-related aspects of uPAR and C4.4A with a view to possible pharmacological targeting strategies for therapy and for non-invasive bioimaging.
Export Options
About this article
Cite this article as:
Jacobsen B. and Ploug M., The Urokinase Receptor and its Structural Homologue C4.4A in Human Cancer: Expression, Prognosis and Pharmacological Inhibition, Current Medicinal Chemistry 2008; 15 (25) . https://dx.doi.org/10.2174/092986708785909012
DOI https://dx.doi.org/10.2174/092986708785909012 |
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
-
Optimizing Anti-EGFR Strategies in Cancer Treatment
Current Cancer Therapy Reviews Anticancer Properties of Essential Oils: An Overview
Current Cancer Drug Targets Down Regulated Expression of Claudin-1 and Claudin-5 and Up Regulation of β-Catenin: Association with Human Glioma Progression
CNS & Neurological Disorders - Drug Targets Modern drug delivery systems for targeting the posterior segment of the eye
Current Pharmaceutical Design Anticancer Drug Sensitivity Testing, a Historical Review and Future Perspectives
Current Drug Therapy Nonbacterial Thrombotic Endocarditis (Marantic Endocarditis) in Cancer Patients
Cardiovascular & Hematological Disorders-Drug Targets Targeting the Hippo Pathway for Anti-cancer Therapies
Current Medicinal Chemistry Threes Company: Regulation of Cell Fate by Statins
Current Drug Targets - Cardiovascular & Hematological Disorders MiRNA, a New Treatment Strategy for Pulmonary Fibrosis
Current Drug Targets Clear Cell Renal Cell Cancer Tumor-Propagating Cells: Molecular Characteristics
Current Signal Transduction Therapy Antitumor Activity of Copper (I)–Nicotinate Complex and Autophagy Modulation in HCC1806 Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Clinical Studies with Targeted Toxins in Malignant Glioma
Reviews on Recent Clinical Trials Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review
Current Genomics Cationic Liposomes for Gene Delivery: Novel Cationic Lipids and Enhancement by Proteins and Peptides
Current Medicinal Chemistry Recent Studies and Biological Aspects of Substantial Indole Derivatives with Anti-cancer Activity
Current Organic Chemistry Current Status and Future of Target-Based Therapeutics
Current Cancer Drug Targets Targeted Therapies in Combination with Radiotherapy in Oesophageal and Gastroesophageal Carcinoma
Current Medicinal Chemistry Differentiation-Inducing Therapy for Solid Tumors
Current Pharmaceutical Design Evaluation of High Risk HPV (HPV-16 and -18) RNA and Integration in Cervical Neoplasms in Systemic Lupus Erythematosus
Current Women`s Health Reviews Intracellular Delivery of Potential Therapeutic Genes: Prospects in Cancer Gene Therapy
Current Gene Therapy