Abstract
Idiopathic pulmonary fibrosis (IPF) and lung cancer share common risk factors, epigenetic and genetic alterations, the activation of similar signaling pathways and poor survival. The aim of this study was to examine the gene expression profiles of stromal cells from patients with IPF and lung adenocarcinoma (ADC) as well as from normal lung. The gene expression levels of cultured stromal cells derived from non-smoking patients with ADC from the tumor (n = 4) and the corresponding normal lung (n = 4) as well as from patients with IPF (n = 4) were investigated with Affymetrix microarrays. The expression of collagen type IV alpha 1 chain, periostin as well as matrix metalloproteinase-1 and -3 in stromal cells and lung tissues were examined with quantitative real-time reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively. Twenty genes were similarly up- or down-regulated in IPF and ADC compared to control, while most of the altered genes in IPF and ADC were differently expressed, including several extracellular matrix genes. Collagen type IV alpha 1 chain as well as matrix metalloproteinases-1 and -3 were differentially expressed in IPF compared to ADC. Periostin was up-regulated in both IPF and ADC in comparison to control. All studied factors were localized by immunohistochemistry in stromal cells within fibroblast foci in IPF and stroma of ADC. Despite the similarities found in gene expressions of IPF and ADC, several differences were also detected, suggesting that the molecular changes occurring in these two lung illnesses are somewhat different.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma of Lung / genetics
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Adenocarcinoma of Lung / metabolism*
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Adenocarcinoma of Lung / pathology
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Aged
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Cell Adhesion Molecules / genetics
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Cells, Cultured
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Collagen Type IV / genetics
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Extracellular Matrix / metabolism
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Extracellular Matrix Proteins / metabolism
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Female
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Fibroblasts / metabolism
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Gene Expression / genetics
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Gene Expression Profiling / methods
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Gene Expression Regulation / genetics
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Humans
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Idiopathic Pulmonary Fibrosis / genetics
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Idiopathic Pulmonary Fibrosis / metabolism*
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Idiopathic Pulmonary Fibrosis / pathology
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Lung / pathology
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Male
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Matrix Metalloproteinase 1 / genetics
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Matrix Metalloproteinase 3 / genetics
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Middle Aged
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Signal Transduction
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Stromal Cells / metabolism*
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Transcriptome / genetics
Substances
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Cell Adhesion Molecules
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Collagen Type IV
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Extracellular Matrix Proteins
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POSTN protein, human
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Matrix Metalloproteinase 3
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MMP1 protein, human
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Matrix Metalloproteinase 1
Grants and funding
R.K. has received grants for the study group from Foundation of the Finnish Anti-Tuberculosis Association, the Research Foundation of the Pulmonary Diseases, Jalmari and Rauha Ahokas Foundation, the Research Foundation of North Finland, and a state subsidy of the Oulu University Hospital. M.K. has received grants for the scientific work from Väinö and Laina Kivi Foundation, the Foundation of the Finnish Anti-Tuberculosis Association, the Tampere Tuberculosis foundation, and the Research Foundation of the Pulmonary Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.