Abstract
Breast cancer is the leading cause of cancer related deaths in women. Most breast cancers stem from mammary ductal cells that secrete nipple aspirate fluid (NAF), a biological sample that contains proteins associated with the tumor microenvironment. In this study, NAF samples from both breasts of 7 Brazilian patients with unilateral breast cancer were analyzed. These samples were systematically compared using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional fluorescence difference gel electrophoresis (2D-DIGE); substantial qualitative individual differences were observed. In general, when NAF samples were compared from both breasts within the same patient their electrophoretic patterns were very similar, regardless of their cancer status. A comparison of all patients identified 2 main NAF protein profiles. The HomEP, homogeneous expression profile, was characterized by typical SDS-PAGE and 2D-DIGE protein patterns that were observed in patients with a good breast cancer prognosis and were similar to previous Type I NAF classifications that used one-dimensional electrophoresis. The HetEP, heterogeneous expression profile, was characterized by distinct protein patterns that have not been reported in previous studies and have been primarily observed in breast cancer patients with a poor prognosis. The NAF samples were rich in metal-dependent proteolytic enzymes, as visualized by SDS-PAGE zymography. They varied qualitatively with respect to their gelatinolytic band distribution. However, there were no correlations between these characteristics and the pathologic features of these tumors. A comparative analysis of NAF samples taken from each breast in a single patient showed conserved zymographic patterns. In conclusion, the present study highlights important distinctions in the protein content of individual NAF samples and provides insight into the composition of the tumor microenvironment. These data reinforce breast cancer as a heterogeneous disease with a diverse natural history, which is becoming increasingly evident through other recent studies.
Keywords: Breast cancer, DIGE, NAF, metalloprotease, proteome.
Current Topics in Medicinal Chemistry
Title:Potential Correlation between Tumor Aggressiveness and Protein Expression Patterns of Nipple Aspirate Fluid (NAF) Revealed by Gel-Based Proteomic Analysis
Volume: 14 Issue: 3
Author(s): Giselle Villa Flor Brunoro, Andre Teixeira da Silva Ferreira, Monique Ramos de Oliveira Trugilho, Tamires Sousa de Oliveira, Luis Claudio Belo Amêndola, Jonas Perales, Richard Hemmi Valente, Claudia Vitória de Moura Gallo, Dante Pagnoncelli and Ana Gisele da Costa Neves-Ferreira
Affiliation:
Keywords: Breast cancer, DIGE, NAF, metalloprotease, proteome.
Abstract: Breast cancer is the leading cause of cancer related deaths in women. Most breast cancers stem from mammary ductal cells that secrete nipple aspirate fluid (NAF), a biological sample that contains proteins associated with the tumor microenvironment. In this study, NAF samples from both breasts of 7 Brazilian patients with unilateral breast cancer were analyzed. These samples were systematically compared using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional fluorescence difference gel electrophoresis (2D-DIGE); substantial qualitative individual differences were observed. In general, when NAF samples were compared from both breasts within the same patient their electrophoretic patterns were very similar, regardless of their cancer status. A comparison of all patients identified 2 main NAF protein profiles. The HomEP, homogeneous expression profile, was characterized by typical SDS-PAGE and 2D-DIGE protein patterns that were observed in patients with a good breast cancer prognosis and were similar to previous Type I NAF classifications that used one-dimensional electrophoresis. The HetEP, heterogeneous expression profile, was characterized by distinct protein patterns that have not been reported in previous studies and have been primarily observed in breast cancer patients with a poor prognosis. The NAF samples were rich in metal-dependent proteolytic enzymes, as visualized by SDS-PAGE zymography. They varied qualitatively with respect to their gelatinolytic band distribution. However, there were no correlations between these characteristics and the pathologic features of these tumors. A comparative analysis of NAF samples taken from each breast in a single patient showed conserved zymographic patterns. In conclusion, the present study highlights important distinctions in the protein content of individual NAF samples and provides insight into the composition of the tumor microenvironment. These data reinforce breast cancer as a heterogeneous disease with a diverse natural history, which is becoming increasingly evident through other recent studies.
Export Options
About this article
Cite this article as:
Brunoro Villa Flor Giselle, Ferreira Teixeira da Silva Andre, Trugilho Ramos de Oliveira Monique, Oliveira Sousa de Tamires, Amêndola Claudio Belo Luis, Perales Jonas, Valente Hemmi Richard, Gallo Vitória de Moura Claudia, Pagnoncelli Dante and Neves-Ferreira Gisele da Costa Ana, Potential Correlation between Tumor Aggressiveness and Protein Expression Patterns of Nipple Aspirate Fluid (NAF) Revealed by Gel-Based Proteomic Analysis, Current Topics in Medicinal Chemistry 2014; 14 (3) . https://dx.doi.org/10.2174/1568026613666131204121854
DOI https://dx.doi.org/10.2174/1568026613666131204121854 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Allelic Imbalances of the egfr Gene as Key Events in Breast Cancer Progression – the Concept of Committed Progenitor Cells
Current Cancer Drug Targets Antioxidant Supplements, Genetics and Chemotherapy Outcomes
Current Cancer Therapy Reviews ErbB Targeted Drugs and Angiogenesis
Current Vascular Pharmacology Nerve Growth Factor Receptors and Signaling in Breast Cancer
Current Cancer Drug Targets An Overview on Fibroblast Growth Factors: Structural, Functional and Therapeutic Implications
Current Proteomics Novel N-mustard-benzimidazoles/benzothiazoles Hybrids, Synthesis and Anticancer Evaluation
Anti-Cancer Agents in Medicinal Chemistry Psychosocial Stress, Emotions and Cytokine-Related Disorders
Recent Patents on Inflammation & Allergy Drug Discovery Therapeutic Targeting of Amyloid Precursor Protein and its Processing Enzymes for Breast Cancer Treatment
Current Protein & Peptide Science A Unique Intracellular, Extracellular and Transmembrane Circulation of Potassium Ions in the Auditory Inner Ear as an Anticarcinogenic Principle? Part 1
Inflammation & Allergy - Drug Targets (Discontinued) Potential Anticancer Effect of Carvacrol Codrugs on Human Glioblastoma Cells
Current Drug Delivery Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Genetic Variation at the Human MGMT Locus and its Biological Consequences
Current Pharmacogenomics PET-MRI Based Molecular Imaging as a Response Marker in Cervical Cancer: A Systematic Review
Current Molecular Imaging (Discontinued) MicroRNA-34a and its target genes: Key factors in cancer multidrug resistance
Current Pharmaceutical Design Role of Glucocorticoids in Breast Cancer
Current Pharmaceutical Design Computer Aided Detection of Clustered Microcalcification: A Survey
Current Medical Imaging The Prognostic Value of Circulating Tumor Cells in Primary Breast Cancer Prior to any Systematic Therapy: A Systematic Review
Current Stem Cell Research & Therapy The Anti-Proliferative Activity of Anisosciadone: A New Guaiane Sesquiterpene from Anisosciadium lanatum
Anti-Cancer Agents in Medicinal Chemistry Bevacizumab and Angiogenesis Inhibitors in the Treatment of CNS Metastases: The Road less Travelled
Current Molecular Pharmacology Clinical Utility of Combined 18F-Fluoro-2-deoxyglucose Positron Emission Tomography – Computed Tomography in the Evaluation of Gastrointestinal Malignancies
Current Medical Imaging