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Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents

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    SYSNO ASEP0457384
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleCharacterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents
    Author(s) Pasdar, E.A. (AU)
    Smits, M. (AU)
    Stapelberg, M. (AU)
    Bajziková, Martina (BTO-N) RID
    Stantic, M. (AU)
    Goodwin, J. (AU)
    Yan, B. (AU)
    Štursa, J. (CZ)
    Kovářová, Jaromíra (BTO-N) RID
    Sachaphibulkij, K. (AU)
    Bezawork-Geleta, A. (AU)
    Sobol, Margaryta (UMG-J) RID
    Philimonenko, Anatoly (UMG-J)
    Tomasetti, M. (IT)
    Zobalová, Renata (BTO-N) RID
    Hozák, Pavel (UMG-J) RID, ORCID
    Dong, L.F. (AU)
    Neužil, Jiří (BTO-N) RID
    Source TitlePLoS ONE. - : Public Library of Science - ISSN 1932-6203
    Roč. 10, č. 5 (2015), e0119549
    Number of pages21 s.
    Languageeng - English
    CountryUS - United States
    KeywordsMALIGNANT PLEURAL MESOTHELIOMA ; EMBRYONIC STEM-CELLS ; ALPHA-TOCOPHERYL SUCCINATE
    Subject RIVEB - Genetics ; Molecular Biology
    R&D ProjectsED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Institutional supportBTO-N - RVO:86652036 ; UMG-J - RVO:68378050
    UT WOS000353887100002
    DOI10.1371/journal.pone.0119549
    AnnotationMalignant mesothelioma (MM) is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs) that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM.
    WorkplaceInstitute of Biotechnology
    ContactMonika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
    Year of Publishing2016
Number of the records: 1  

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