Abstract
Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with further activation in tumors, paralleled by increased levels of cells with nuclear YAP/TAZ. Arg1 was one of the highest upregulated genes in inflamed tissue and tumor. Inflamed tissue showed increased levels of single-nucleotide variations, with an RNA-editing signature, which were even higher in the tumor samples. Subcutaneous injection of asbestos-treated, but tumor-free mice with syngeneic mesothelioma tumor cells resulted in a significantly higher incidence of tumor growth when compared to naïve mice supporting the role of the environment in tumor progression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Asbestos, Crocidolite / adverse effects*
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Gene Regulatory Networks*
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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Lung Neoplasms / chemically induced
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Lung Neoplasms / genetics*
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Lung Neoplasms / metabolism
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Macrophage Activation
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Mesothelioma / chemically induced
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Mesothelioma / genetics*
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Mesothelioma / metabolism
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Mesothelioma, Malignant
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Mice
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Mutation
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Phosphoproteins
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Polymorphism, Single Nucleotide
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RNA Editing*
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Trans-Activators
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Transcription Factors
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Transcriptional Activation*
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Intracellular Signaling Peptides and Proteins
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Phosphoproteins
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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WWTR1 protein, human
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YAP-Signaling Proteins
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YAP1 protein, human
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Asbestos, Crocidolite