Plasticity of fibroblasts demonstrated by tissue-specific and function-related proteome profiling

Clinical Proteomics

Anastasia Meshcheryakova⁴  Hendrik Jan Ankersmit⁵  Christopher Gerner¹  Verena Paulitschke³  Agnes Beer⁴  Astrid Slany² 

[1] Faculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Vienna, AustriaDepartment of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, AustriaFaculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Vienna, AustriaFaculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Vienna, AustriaDepartment of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, AustriaDepartment of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, AustriaFaculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Vienna, AustriaDepartment of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, Austria;Faculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Vienna, AustriaFaculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Vienna, AustriaFaculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Vienna, Austria;Department of Dermatology, Medical University of Vienna, Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, Vienna, Austria;Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, AustriaDepartment of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, AustriaDepartment of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, Austria;Department of Thoracic Surgery, Division of Surgery, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, AustriaDepartment of Thoracic Surgery, Division of Surgery, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, AustriaDepartment of Thoracic Surgery, Division of Surgery, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University Vienna, Vienna, Austria

关键词: Fibroblasts;    Inflammatory activation;    Tumor-stroma interactions;    Primary human cells;    Proteome profiling;   

DOI  :  10.1186/1559-0275-11-41

来源: Humana Press Inc

【 摘 要 】

Abstract

Background

Fibroblasts are mesenchymal stromal cells which occur in all tissue types. While their main function is related to ECM production and physical support, they are also important players in wound healing, and have further been recognized to be able to modulate inflammatory processes and support tumor growth. Fibroblasts can display distinct phenotypes, depending on their tissue origin, as well as on their functional state.

Results

In order to contribute to the proteomic characterization of fibroblasts, we have isolated primary human fibroblasts from human skin, lung and bone marrow and generated proteome profiles of these cells by LC-MS/MS. Comparative proteome profiling revealed characteristic differences therein, which seemed to be related to the cell’s tissue origin. Furthermore, the cells were treated in vitro with the pro-inflammatory cytokine IL-1beta. While all fibroblasts induced the secretion of Interleukins IL-6 and IL-8 and the chemokine GRO-alpha, other inflammation-related proteins were up-regulated in an apparently tissue-dependent manner. Investigating fibroblasts from tumorous tissues of skin, lung and bone marrow with respect to such inflammation-related proteins revealed hardly any conformity but rather individual and tumor type-related variations. However, apparent up-regulation of IGF-II, PAI-1 and PLOD2 was observed in melanoma-, lung adenocarcinoma- and multiple myeloma-associated fibroblasts, as well as in hepatocellular carcinoma-associated fibroblasts.

Conclusions

Inflammation-related proteome alterations of primary human fibroblasts were determined by the analysis of IL-1beta treated cells. Tumor-associated fibroblasts from different tissue types hardly showed signs of acute inflammation but displayed characteristic functional aberrations potentially related to chronic inflammation. The present data suggest that the state of the tumor microenvironment is relevant for tumor progression and targeted treatment of tumor-associated fibroblasts may support anti-cancer strategies.

【 授权许可】

Unknown