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TLR4-Mediated Recognition of Mouse Polyomavirus Promotes Cancer-Associated Fibroblast-Like Phenotype and Cell Invasiveness
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SYSNO ASEP 0542160 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title TLR4-Mediated Recognition of Mouse Polyomavirus Promotes Cancer-Associated Fibroblast-Like Phenotype and Cell Invasiveness Author(s) Janovec, Václav (UOCHB-X) ORCID, RID
Ryabchenko, B. (CZ)
Škarková, A. (CZ)
Pokorná, Karolína (UOCHB-X) ORCID
Rösel, D. (CZ)
Brábek, J. (CZ)
Weber, Jan (UOCHB-X) RID, ORCID
Forstová, J. (CZ)
Hirsch, Ivan (UOCHB-X) ORCID, RID
Huérfano, S. (CZ)Article number 2076 Source Title Cancers (Basel). - : MDPI
Roč. 13, č. 9 (2021)Number of pages 16 s. Language eng - English Country CH - Switzerland Keywords mouse polyomavirus ; MPyV ; mouse fibroblasts ; CAF ; TLR4 ; IL-6 ; spheroid invasiveness OECD category Virology Research Infrastructure Czech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i. Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 000649905400001 EID SCOPUS 85104574550 DOI 10.3390/cancers13092076 Annotation The tumorigenic potential of mouse polyomavirus (MPyV) has been studied for decades in cell culture models and has been mainly attributed to nonstructural middle T antigen (MT), which acts as a scaffold signal adaptor, activates Src tyrosine kinases, and possesses transforming ability. We hypothesized that MPyV could also transform mouse cells independent of MT via a Toll-like receptor 4 (TLR4)-mediated inflammatory mechanism. To this end, we investigated the interaction of MPyV with TLR4 in mouse embryonic fibroblasts (MEFs) and 3T6 cells, resulting in secretion of interleukin 6 (IL-6), independent of active viral replication. TLR4 colocalized with MPyV capsid protein VP1 in MEFs. Neither TLR4 activation nor recombinant IL-6 inhibited MPyV replication in MEFs and 3T6 cells. MPyV induced STAT3 phosphorylation through both direct and MT-dependent and indirect and TLR4/IL-6-dependent mechanisms. We demonstrate that uninfected mouse fibroblasts exposed to the cytokine environment from MPyV-infected fibroblasts upregulated the expressions of MCP-1, CCL-5, and α-SMA. Moreover, the cytokine microenvironment increased the invasiveness of MEFs and CT26 carcinoma cells. Collectively, TLR4 recognition of MPyV induces a cytokine environment that promotes the cancer-associated fibroblast (CAF)-like phenotype in noninfected fibroblasts and increases cell invasiveness. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Year of Publishing 2022 Electronic address https://doi.org/10.3390/cancers13092076
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