ACS Publications. Most Trusted. Most Cited. Most Read
Proteome Profiling of Breast Cancer Biopsies Reveals a Wound Healing Signature of Cancer-Associated Fibroblasts
My Activity

Figure 1Loading Img
    Article

    Proteome Profiling of Breast Cancer Biopsies Reveals a Wound Healing Signature of Cancer-Associated Fibroblasts
    Click to copy article linkArticle link copied!

    View Author Information
    Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Währingerstr. 38, Vienna A-1090, Austria
    Department of Medicine I, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, Spitalgasse 23, Vienna A-1090, Austria
    § Department of Clinical Pharmacy and Diagnostics, University of Vienna, Althanstrasse 14, Vienna A-1090, Austria
    Division of Special Gynaecology, Department of Obstetrics and Gynecology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna A-1090, Austria
    *E-mail: [email protected]. Tel: +43-1-4277-52302.
    Other Access OptionsSupporting Information (5)

    Journal of Proteome Research

    Cite this: J. Proteome Res. 2014, 13, 11, 4773–4782
    Click to copy citationCitation copied!
    https://doi.org/10.1021/pr500727h
    Published September 19, 2014
    Copyright © 2014 American Chemical Society

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study, we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near, and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. All mass analysis data have been made fully accessible via ProteomeXchange, DOI PXD001311 and PXD001323-8. Comparison of tissue proteomics data with all of those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1, and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.

    Copyright © 2014 American Chemical Society

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    Table S1. Assignment of PRIDE Identifiers and DOIs to the corresponding data set. Table S2. Proteins identified in tissue biopsies and their regulation between tumor-central and tumor-distant tissues. Table S3. Proteins identified in ZR-75-1. Table S4. Proteins identified in control HMFs. Table S5. Protein regulation in IL-1β and TGFβ treated HMFs. This material is available free of charge via the Internet at http://pubs.acs.org.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai

    This article is cited by 28 publications.

    1. Regine C. Tölle, Cedric Gaggioli, Jörn Dengjel. Three-Dimensional Cell Culture Conditions Affect the Proteome of Cancer-Associated Fibroblasts. Journal of Proteome Research 2018, 17 (8) , 2780-2789. https://doi.org/10.1021/acs.jproteome.8b00237
    2. Ammar Tahir, Andrea Bileck, Besnik Muqaku, Laura Niederstaetter, Dominique Kreutz, Rupert L. Mayer, Denise Wolrab, Samuel M. Meier, Astrid Slany, and Christopher Gerner . Combined Proteome and Eicosanoid Profiling Approach for Revealing Implications of Human Fibroblasts in Chronic Inflammation. Analytical Chemistry 2017, 89 (3) , 1945-1954. https://doi.org/10.1021/acs.analchem.6b04433
    3. Visith Thongboonkerd , Joshua LaBaer , Gilberto B. Domont . Recent Advances of Proteomics Applied to Human Diseases. Journal of Proteome Research 2014, 13 (11) , 4493-4496. https://doi.org/10.1021/pr501038g
    4. Lukas Janker, Dina Schuster, Patricia Bortel, Gerhard Hagn, Samuel M Meier-Menches, Thomas Mohr, Johanna C Mader, Astrid Slany, Andrea Bileck, Julia Brunmair, Christian Madl, Lukas Unger, Barbara Hennlich, Barbara Weitmayr, Giorgia Del Favero, Dietmar Pils, Tobias Pukrop, Nikolaus Pfisterer, Thomas Feichtenschlager, Christopher Gerner. Multiomics-empowered Deep Phenotyping of Ulcerative Colitis Identifies Biomarker Signatures Reporting Functional Remission States. Journal of Crohn's and Colitis 2023, 17 (9) , 1514-1527. https://doi.org/10.1093/ecco-jcc/jjad052
    5. Marina Sourouni, Carl Opitz, Isabel Radke, Ludwig Kiesel, Joke Tio, Martin Götte, Marie‐Kristin von Wahlde. Establishment of a 3D co‐culture model to investigate the role of primary fibroblasts in ductal carcinoma in situ of the breast. Cancer Reports 2023, 6 (4) https://doi.org/10.1002/cnr2.1771
    6. Katie M. Hamel, Kara Q. Liimatta, Jorge A. Belgodere, Bruce A. Bunnell, Jeffrey M. Gimble, Elizabeth C. Martin. Adipose-Derived Stromal/Stem Cell Response to Tumors and Wounds: Evaluation of Patient Age. Stem Cells and Development 2022, 31 (19-20) , 579-592. https://doi.org/10.1089/scd.2021.0280
    7. Lukas Janker, Dina Schuster, Patricia Bortel, Gerhard Hagn, Julia Brunmair, Samuel M. Meier-Menches, Johanna C. Mader, Astrid Slany, Andrea Bileck, Christian Madl, Lukas Unger, Barbara Hennlich, Barbara Weitmayr, Giorgia Del Favero, Dietmar Pils, Tobias Pukrop, Nikolaus Pfisterer, Thomas Feichtenschlager, Christopher Gerner. Multi-omics empowered deep phenotyping of ulcerative colitis. 2022https://doi.org/10.1101/2022.05.25.22275502
    8. Lu Han, Cara Seward, Gustavo Leone, Michael C. Ostrowski. Origin, activation and heterogeneity of fibroblasts associated with pancreas and breast cancers. 2022, 169-201. https://doi.org/10.1016/bs.acr.2022.03.003
    9. Tamara Weiss, Sabine Taschner-Mandl, Lukas Janker, Andrea Bileck, Fikret Rifatbegovic, Florian Kromp, Helena Sorger, Maximilian O. Kauer, Christian Frech, Reinhard Windhager, Christopher Gerner, Peter F. Ambros, Inge M. Ambros. Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-21859-0
    10. Jing Lv, Meiqiang Xie, Shufen Zhao, Wensheng Qiu, Shasha Wang, Manming Cao. Synergetic fabrication of hybrid drug formulation using biodegradable tri-block copolymeric liquid nanoparticle delivery for gastric cancer chemotherapy. Journal of Molecular Liquids 2021, 340 , 117066. https://doi.org/10.1016/j.molliq.2021.117066
    11. Marlene C. Gerner, Andrea Bileck, Lukas Janker, Liesa S. Ziegler, Thomas Öhlinger, Pierre Raeven, Ernst W. Müllner, Ulrich Salzer, Christopher Gerner, Klaus G. Schmetterer, David M. Baron. Packed red blood cells inhibit T-cell activation via ROS-dependent signaling pathways. Journal of Biological Chemistry 2021, 296 , 100487. https://doi.org/10.1016/j.jbc.2021.100487
    12. Jeffrey M. Dick. Water as a reactant in the differential expression of proteins in cancer. 2020https://doi.org/10.1101/2020.04.09.035022
    13. Tamara Weiss, Sabine Taschner-Mandl, Andrea Bileck, Fikret Rifatbegovic, Helena Sorger, Max Kauer, Christian Frech, Reinhard Windhager, Christopher Gerner, Peter F. Ambros, Inge M Ambros. Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8. 2020https://doi.org/10.1101/2020.04.01.019422
    14. Besnik Muqaku, Dietmar Pils, Johanna C. Mader, Stefanie Aust, Andreas Mangold, Liridon Muqaku, Astrid Slany, Giorgia Del Favero, Christopher Gerner. Neutrophil Extracellular Trap Formation Correlates with Favorable Overall Survival in High Grade Ovarian Cancer. Cancers 2020, 12 (2) , 505. https://doi.org/10.3390/cancers12020505
    15. Besnik Muqaku, Dietmar Pils, Johanna C. Mader, Stefanie Aust, Andreas Mangold, Liridon Muqaku, Astrid Slany, Giorgia Del Favero, Christopher Gerner. Neutrophil extracellular trap formation correlates with improved overall survival in ovarian cancer. 2019https://doi.org/10.1101/862292
    16. Lukas Janker, Rupert L. Mayer, Andrea Bileck, Dominique Kreutz, Johanna C. Mader, Kirsten Utpatel, Daniel Heudobler, Hermine Agis, Christopher Gerner, Astrid Slany. Metabolic, Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia*. Molecular & Cellular Proteomics 2019, 18 (5) , 936a-953. https://doi.org/10.1074/mcp.RA119.001390
    17. Kousuke Sasaki, Tamotsu Sugai, Kazuyuki Ishida, Mitsumasa Osakabe, Hiroo Amano, Hiroaki Kimura, Minoru Sakuraba, Katsuhiko Kashiwa, Seiichiro Kobayashi. Analysis of cancer-associated fibroblasts and the epithelial-mesenchymal transition in cutaneous basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Human Pathology 2018, 79 , 1-8. https://doi.org/10.1016/j.humpath.2018.03.006
    18. Dominique Kreutz, Chomdao Sinthuvanich, Andrea Bileck, Lukas Janker, Besnik Muqaku, Astrid Slany, Christopher Gerner. Curcumin exerts its antitumor effects in a context dependent fashion. Journal of Proteomics 2018, 182 , 65-72. https://doi.org/10.1016/j.jprot.2018.05.007
    19. Antigoni Manousopoulou, Annette Hayden, Massimiliano Mellone, Diana J. Garay-Baquero, Cory H. White, Fergus Noble, Monette Lopez, Gareth J. Thomas, Timothy J. Underwood, Spiros D. Garbis. Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma. British Journal of Cancer 2018, 118 (9) , 1200-1207. https://doi.org/10.1038/s41416-018-0042-9
    20. Halh Al-Serori, Franziska Ferk, Michael Kundi, Andrea Bileck, Christopher Gerner, Miroslav Mišík, Armen Nersesyan, Monika Waldherr, Manuel Murbach, Tamara T. Lah, Christel Herold-Mende, Andrew R. Collins, Siegfried Knasmüller, . Mobile phone specific electromagnetic fields induce transient DNA damage and nucleotide excision repair in serum-deprived human glioblastoma cells. PLOS ONE 2018, 13 (4) , e0193677. https://doi.org/10.1371/journal.pone.0193677
    21. Alice Santi, Fernanda G. Kugeratski, Sara Zanivan. Cancer Associated Fibroblasts: The Architects of Stroma Remodeling. PROTEOMICS 2018, 18 (5-6) https://doi.org/10.1002/pmic.201700167
    22. Rupert L. Mayer, Josef D. Schwarzmeier, Marlene C. Gerner, Andrea Bileck, Johanna C. Mader, Samuel M. Meier-Menches, Samuel M. Gerner, Klaus G. Schmetterer, Tobias Pukrop, Albrecht Reichle, Astrid Slany, Christopher Gerner. Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia. Molecular & Cellular Proteomics 2018, 17 (2) , 290-303. https://doi.org/10.1074/mcp.RA117.000425
    23. Daniel Drev, Andrea Bileck, Zeynep N. Erdem, Thomas Mohr, Gerald Timelthaler, Andrea Beer, Christopher Gerner, Brigitte Marian. Proteomic profiling identifies markers for inflammation-related tumor–fibroblast interaction. Clinical Proteomics 2017, 14 (1) https://doi.org/10.1186/s12014-017-9168-7
    24. Tamara Weiss, Sabine Taschner-Mandl, Andrea Bileck, Astrid Slany, Florian Kromp, Fikret Rifatbegovic, Christian Frech, Reinhard Windhager, Hugo Kitzinger, Chieh-Han Tzou, Peter F. Ambros, Christopher Gerner, Inge M. Ambros. Proteomics and transcriptomics of peripheral nerve tissue and cells unravel new aspects of the human Schwann cell repair phenotype. Glia 2016, 64 (12) , 2133-2153. https://doi.org/10.1002/glia.23045
    25. Meredith C. Henderson, Alan B. Hollingsworth, Kelly Gordon, Michael Silver, Rao Mulpuri, Elias Letsios, David E. Reese, . Integration of Serum Protein Biomarker and Tumor Associated Autoantibody Expression Data Increases the Ability of a Blood-Based Proteomic Assay to Identify Breast Cancer. PLOS ONE 2016, 11 (8) , e0157692. https://doi.org/10.1371/journal.pone.0157692
    26. Liu Liu, Lin Liu, Han Hui Yao, Zhi Qiang Zhu, Zhong Liang Ning, Qiang Huang, . Stromal Myofibroblasts Are Associated with Poor Prognosis in Solid Cancers: A Meta-Analysis of Published Studies. PLOS ONE 2016, 11 (7) , e0159947. https://doi.org/10.1371/journal.pone.0159947
    27. Xuebing Liang, Yang Wang, Lauren Franzblau, Jiguang Ma. Potential Safety Loophole of Fat Grafting in Breast Cancer Patients. Aesthetic Plastic Surgery 2016, 40 (3) , 380-386. https://doi.org/10.1007/s00266-016-0634-9
    28. Astrid Slany, Andrea Bileck, Dominique Kreutz, Rupert L. Mayer, Besnik Muqaku, Christopher Gerner. Contribution of Human Fibroblasts and Endothelial Cells to the Hallmarks of Inflammation as Determined by Proteome Profiling. Molecular & Cellular Proteomics 2016, 15 (6) , 1982-1997. https://doi.org/10.1074/mcp.M116.058099
    29. Roman Šmidák, Rupert Laurenz Mayer, Andrea Bileck, Christopher Gerner, Diana Mechtcheriakova, Oliver Stork, Gert Lubec, Lin Li. Quantitative proteomics reveals protein kinases and phosphatases in the individual phases of contextual fear conditioning in the C57BL/6J mouse. Behavioural Brain Research 2016, 303 , 208-217. https://doi.org/10.1016/j.bbr.2015.12.033
    30. Fransisca Leonard, Biana Godin. Nanocarrier-Based Anticancer Therapies with the Focus on Strategies for Targeting the Tumor Microenvironment. 2016, 67-122. https://doi.org/10.1007/978-3-319-43525-1_4
    31. Astrid Slany, Andrea Bileck, Besnik Muqaku, Christopher Gerner. Targeting breast cancer-associated fibroblasts to improve anti-cancer therapy. The Breast 2015, 24 (5) , 532-538. https://doi.org/10.1016/j.breast.2015.06.009
    32. Joana Simões, Francisco M. Amado, Rui Vitorino, Luisa A. Helguero. A meta-analysis to evaluate the cellular processes regulated by the interactome of endogenous and over-expressed estrogen receptor alpha. Oncoscience 2015, 2 (5) , 487-496. https://doi.org/10.18632/oncoscience.138

    Journal of Proteome Research

    Cite this: J. Proteome Res. 2014, 13, 11, 4773–4782
    Click to copy citationCitation copied!
    https://doi.org/10.1021/pr500727h
    Published September 19, 2014
    Copyright © 2014 American Chemical Society

    Article Views

    1638

    Altmetric

    -

    Citations

    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.