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Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents
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SYSNO ASEP 0457384 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Characterisation 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) RIDSource Title PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 10, č. 5 (2015), e0119549Number of pages 21 s. Language eng - English Country US - United States Keywords MALIGNANT PLEURAL MESOTHELIOMA ; EMBRYONIC STEM-CELLS ; ALPHA-TOCOPHERYL SUCCINATE Subject RIV EB - Genetics ; Molecular Biology R&D Projects ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000353887100002 DOI 10.1371/journal.pone.0119549 Annotation Malignant 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2016
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