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

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.

SUBMITTER: Slany A

PROVIDER: S-EPMC4448269 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Slany Astrid A Meshcheryakova Anastasia A Beer Agnes A Ankersmit Hendrik Jan HJ Paulitschke Verena V Gerner Christopher C

Clinical proteomics 20141121 1

<h4>Background</h4>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.<h4>Results</h4>In order to contribute to the proteomic ch ...[more]

PMID: 26029019

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Project description:Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this "guilt-by-association" (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies.

Dataset Information

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

Publications

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

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