Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4 + CD25 + FoxP3 + regulatory T cells activation.

Autor:	Lo Re O; International Clinical Research Center, St' Anne's University Hospital, Brno, Czech Republic.; Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic., Mazza T; IRCCS Casa Sollievo della Sofferenza, Laboratory of Bioinformatics, San Giovanni Rotondo (FG), Italy., Giallongo S; International Clinical Research Center, St' Anne's University Hospital, Brno, Czech Republic.; Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic., Sanna P; International Clinical Research Center, St' Anne's University Hospital, Brno, Czech Republic., Rappa F; Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy., Vinh Luong T; Department of Histopathology, Royal Free London NHS Foundation Trust, London, United Kingdom., Li Volti G; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Drovakova A; Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.; Department of Animal Physiology and Immunology, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic., Roskams T; Translational Cell & Tissue Research Unit, Department of Imaging & Pathology, Katholieke Universiteit Leuven, Leuven, Belgium., Van Haele M; Translational Cell & Tissue Research Unit, Department of Imaging & Pathology, Katholieke Universiteit Leuven, Leuven, Belgium., Tsochatzis E; UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom., Vinciguerra M; International Clinical Research Center, St' Anne's University Hospital, Brno, Czech Republic.; UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2020 Jan 01; Vol. 10 (2), pp. 910-924. Date of Electronic Publication: 2020 Jan 01 (Print Publication: 2020).
DOI:	10.7150/thno.35045
Abstrakt:	Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4 + /CD25 + /FoxP3 + T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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