Abstract
The urokinase-type plasminogen activator (uPA) and its main inhibitor PAI-1 play key roles in tumorassociated processes such as the degradation of the extracellular matrix (ECM), tissue remodeling, cell adhesion and migration. Elevated expression of both molecules is known to correlate with negative outcomes in node negative breast cancer. To date, these molecules are the only prognostic markers to have reached the highest level of evidence (LOE I) in multi-centered clinical trials for prognosis of node negative breast cancer. Unfortunately, the clinical utility of these molecules as markers is limited by the use of enzyme-linked immunoassay (ELISA) tests for their detection. The ELISA relies on the use of fresh or frozen tissue, which are rarely available in routine clinical settings. In this review article, we provide an overview of the clinical relevance of uPA and PAI-1 and present alternative methods for their detection. Common uPA and PAI-1 detection methods discussed in literature include RT-PCR-based assays and classical immunohistochemistry approaches. In recent years, attempts have been made to isolate and analyze proteins of formalin fixed, paraffin embedded (FFPE) tissues. These new methods are of special interest because up to now neither RT-PCR nor immunohistochemistry are recommended for the detection of uPA and PAI-1. Here, we present an approach for the analysis of uPA and PAI-1 directly from FFPE tissues that may eventually overcome the limitations of current assays and make the use of both markers widely available for routine prognosis and therapy decisions for breast cancer patients.
Keywords: Formalin fixed, paraffin embedded tissue (FFPE), highest level of evidence (LOE I), invasion, migration, plasminogen activator inhibitor 1 (PAI-1), Urokinase-type plasminogen activator (uPA), extracellular matrix, LOE I, ELISA, RT-PCR, DFS, OS, chemotherapy, EORTC-RBG, lymph node, RFS, Her2, VEGF, ASCO, IHC, SDS-PAGE, Immunoblotting, RPPA, RPMA, NDME, RNA, protein, immunohistochemistry, proteins, Coomassie staining, formalin, cancer, DTT, SDS, Western blot, Reverse Phase Protein Mircoarray, ER, PR
Current Medicinal Chemistry
Title: UPA and PAI-1 Analysis from Fixed Tissues – New Perspectives for a Known Set of Predictive Markers
Volume: 17 Issue: 35
Author(s): K. Malinowsky, C. Bollner, S. Hipp, D. Berg, M. Schmitt and K. F. Becker
Affiliation:
Keywords: Formalin fixed, paraffin embedded tissue (FFPE), highest level of evidence (LOE I), invasion, migration, plasminogen activator inhibitor 1 (PAI-1), Urokinase-type plasminogen activator (uPA), extracellular matrix, LOE I, ELISA, RT-PCR, DFS, OS, chemotherapy, EORTC-RBG, lymph node, RFS, Her2, VEGF, ASCO, IHC, SDS-PAGE, Immunoblotting, RPPA, RPMA, NDME, RNA, protein, immunohistochemistry, proteins, Coomassie staining, formalin, cancer, DTT, SDS, Western blot, Reverse Phase Protein Mircoarray, ER, PR
Abstract: The urokinase-type plasminogen activator (uPA) and its main inhibitor PAI-1 play key roles in tumorassociated processes such as the degradation of the extracellular matrix (ECM), tissue remodeling, cell adhesion and migration. Elevated expression of both molecules is known to correlate with negative outcomes in node negative breast cancer. To date, these molecules are the only prognostic markers to have reached the highest level of evidence (LOE I) in multi-centered clinical trials for prognosis of node negative breast cancer. Unfortunately, the clinical utility of these molecules as markers is limited by the use of enzyme-linked immunoassay (ELISA) tests for their detection. The ELISA relies on the use of fresh or frozen tissue, which are rarely available in routine clinical settings. In this review article, we provide an overview of the clinical relevance of uPA and PAI-1 and present alternative methods for their detection. Common uPA and PAI-1 detection methods discussed in literature include RT-PCR-based assays and classical immunohistochemistry approaches. In recent years, attempts have been made to isolate and analyze proteins of formalin fixed, paraffin embedded (FFPE) tissues. These new methods are of special interest because up to now neither RT-PCR nor immunohistochemistry are recommended for the detection of uPA and PAI-1. Here, we present an approach for the analysis of uPA and PAI-1 directly from FFPE tissues that may eventually overcome the limitations of current assays and make the use of both markers widely available for routine prognosis and therapy decisions for breast cancer patients.
Export Options
About this article
Cite this article as:
Malinowsky K., Bollner C., Hipp S., Berg D., Schmitt M. and F. Becker K., UPA and PAI-1 Analysis from Fixed Tissues – New Perspectives for a Known Set of Predictive Markers, Current Medicinal Chemistry 2010; 17 (35) . https://dx.doi.org/10.2174/092986710793361216
DOI https://dx.doi.org/10.2174/092986710793361216 |
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
-
Panobinostat: The Small Molecule Metalloenzyme Inhibitor with Marvelous Anticancer Activity
Current Topics in Medicinal Chemistry Identifying Candidates for Breast Cancer using Interactions of Chemicals and Proteins
Combinatorial Chemistry & High Throughput Screening Blockers of Voltage-Gated Sodium Channels for the Treatment of Central Nervous System Diseases
Recent Patents on CNS Drug Discovery (Discontinued) CD147/EMMPRIN and CD44 are Potential Therapeutic Targets for Metastatic Prostate Cancer
Current Cancer Drug Targets Adipokines in Arthritis: New Kids on the Block
Current Rheumatology Reviews Single Nucleotide Polymorphisms in Colitis-Associated Colorectal Cancer: A Current Overview with Emphasis on the Role of the Associated Genes Products
Current Drug Targets The Role of TNFSF15 in the Modulation of Neovascularization and Inflammation
Current Hypertension Reviews Hemangiomas, Angiosarcomas, and Vascular Malformations Represent the Signaling Abnormalities of Pathogenic Angiogenesis
Current Molecular Medicine Impact of MCP -1 in Atherosclerosis
Current Pharmaceutical Design Biomimetic Drug Delivery Systems Oriented by Biological Function in Tumor Targeting
Current Drug Targets Benzofuran: A Key Heterocycle - Ring Closure And Beyond
Mini-Reviews in Organic Chemistry Novel Anthraquinone Derivatives as Dual Inhibitors of Topoisomerase 2 and Casein Kinase 2: In Silico Studies, Synthesis and Biological Evaluation on Leukemic Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Histone Deacetylase Inhibitors: Potent Anti-Leukemic Agents
Current Medicinal Chemistry Cystic Hygroma with Multiple Benign Bone Lymphangiomas in an Adult Patient: A Rare Entity in the Differential Diagnosis of Multiple Osseous Lesions in Oncology Practice
Current Medical Imaging Intestinal Absorption and Presystemic Elimination of Various Chemical Constituents Present in GBE50 Extract, a Standardized Extract of Ginkgo biloba Leaves
Current Drug Metabolism lGnRH-III - a Promising Candidate for Anticancer Drug Development
Protein & Peptide Letters Modification of Decoy Oligodeoxynucleotides to Achieve the Stability and Therapeutic Efficacy
Current Topics in Medicinal Chemistry Oleuropein Mediated Targeting of Signaling Network in Cancer
Current Topics in Medicinal Chemistry Effects of Peptidic Antagonists of Grb2-SH2 on Human Breast Cancer Cells
Protein & Peptide Letters Effect of Neuroinflammation on ABC Transporters: Possible Contribution to Refractory Epilepsy
CNS & Neurological Disorders - Drug Targets