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Transcriptional and phenotypical alterations associated with a gradual benzo[a]pyrene-induced transition of human bronchial epithelial cells into mesenchymal-like cells

M. Hýžďalová, J. Procházková, N. Straková, K. Pěnčíková, S. Strapáčová, J. Slováčková, S. Kajabová, H. Líbalová, J. Topinka, M. Kabátková, J. Vondráček, S. Mollerup, M. Machala

. 2024 ; 107 (-) : 104424. [pub] 20240322

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24014425

The role of benzo[a]pyrene (BaP), a prominent genotoxic carcinogen and aryl hydrocarbon receptor (AhR) ligand, in tumor progression remains poorly characterized. We investigated the impact of BaP on the process of epithelial-mesenchymal transition (EMT) in normal human bronchial epithelial HBEC-12KT cells. Early morphological changes after 2-week exposure were accompanied with induction of SERPINB2, IL1, CDKN1A/p21 (linked with cell cycle delay) and chemokine CXCL5. After 8-week exposure, induction of cell migration and EMT-related pattern of markers/regulators led to induction of further pro-inflammatory cytokines or non-canonical Wnt pathway ligand WNT5A. This trend of up-regulation of pro-inflammatory genes and non-canonical Wnt pathway constituents was observed also in the BaP-transformed HBEC-12KT-B1 cells. In general, transcriptional effects of BaP differed from those of TGFβ1, a prototypical EMT inducer, or a model non-genotoxic AhR ligand, TCDD. Carcinogenic polycyclic aromatic hydrocarbons could thus induce a unique set of molecular changes linked with EMT and cancer progression.

Citace poskytuje Crossref.org

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$a Transcriptional and phenotypical alterations associated with a gradual benzo[a]pyrene-induced transition of human bronchial epithelial cells into mesenchymal-like cells / $c M. Hýžďalová, J. Procházková, N. Straková, K. Pěnčíková, S. Strapáčová, J. Slováčková, S. Kajabová, H. Líbalová, J. Topinka, M. Kabátková, J. Vondráček, S. Mollerup, M. Machala
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$a The role of benzo[a]pyrene (BaP), a prominent genotoxic carcinogen and aryl hydrocarbon receptor (AhR) ligand, in tumor progression remains poorly characterized. We investigated the impact of BaP on the process of epithelial-mesenchymal transition (EMT) in normal human bronchial epithelial HBEC-12KT cells. Early morphological changes after 2-week exposure were accompanied with induction of SERPINB2, IL1, CDKN1A/p21 (linked with cell cycle delay) and chemokine CXCL5. After 8-week exposure, induction of cell migration and EMT-related pattern of markers/regulators led to induction of further pro-inflammatory cytokines or non-canonical Wnt pathway ligand WNT5A. This trend of up-regulation of pro-inflammatory genes and non-canonical Wnt pathway constituents was observed also in the BaP-transformed HBEC-12KT-B1 cells. In general, transcriptional effects of BaP differed from those of TGFβ1, a prototypical EMT inducer, or a model non-genotoxic AhR ligand, TCDD. Carcinogenic polycyclic aromatic hydrocarbons could thus induce a unique set of molecular changes linked with EMT and cancer progression.
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$a Procházková, Jiřina $u Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 70, Brno 62100, Czech Republic; Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Kralovopolska 135, Brno 61200, Czech Republic
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$a Straková, Nicol $u Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 70, Brno 62100, Czech Republic
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$a Pěnčíková, Kateřina $u Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 70, Brno 62100, Czech Republic
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$a Strapáčová, Simona $u Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 70, Brno 62100, Czech Republic
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$a Slováčková, Jana $u Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 70, Brno 62100, Czech Republic; Department of Histology and Embryology, Masaryk University, Kamenice 3, Brno 62500, Czech Republic
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$a Kajabová, Simona $u Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 70, Brno 62100, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
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$a Líbalová, Helena $u Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, Prague 142 20, Czech Republic
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$a Topinka, Jan $u Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, Prague 142 20, Czech Republic
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$a Kabátková, Markéta $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Kralovopolska 135, Brno 61200, Czech Republic
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$a Mollerup, Steen $u Research Group for Occupational Toxicology, The National Institute of Occupational Health in Norway, Oslo 0304, Norway
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