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bioRxiv · 10.1101/182980

How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing and somatic mutations

Rehrauer, H.·Wu, L.·Blum, W.·Pecze, L.·Henzi, T.·Serre-Beinier, V.·Aquino, C.·Vrugt, B.·de Perrot, M.·Schwaller, B.·Felley-Bosco, E.
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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 naive mice supporting the role of the environment in tumor progression.\n\nHighlightsO_LIAsbestos increases levels of cytokines and growth factors in mesothelium environment\nC_LIO_LIRecruitment of macrophages and mesothelial precursor cells prior to tumor development\nC_LIO_LIYAP/TAZ signaling upregulated in pre-neoplastic tissues and cancer\nC_LIO_LIIncreased RNA-editing and somatic mutations as early steps in tumor development\nC_LI

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Rehrauer, H., Wu, L., Blum, W., Pecze, L., Henzi, T., Serre-Beinier, V., Aquino, C., Vrugt, B., de Perrot, M., Schwaller, B., Felley-Bosco, E.. 2017-08-31. How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing and somatic mutations. https://doi.org/10.1101/182980

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