Identification and characterisation of NANOG+/ OCT-4<sup>high</sup>/SOX2+ doxorubicin-resistant stem-like cells from transformed trophoblastic cell lines
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Authors
Balahmar, Reham M.Boocock, David J.
Coveney, Clare
Ray, Sankalita
Vadakekolathu, Jayakumar
Regad, Tarik
Ali, Selman
Sivasubramaniam, Shiva
Affiliation
Nottingham Trent UniversityIssue Date
2018-01-11
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Treatment of gestational trophoblastic diseases (GTD) involves surgery, radiotherapy and chemotherapy. Although, these therapeutic approaches are highly successful, drug resistance and toxicity remain a concern for high risk patients. This Chemoresistance has also been observed in the presence of cancer stem cells that are thought to be responsible for cases of cancer recurrence. In this study, we report the presence of previously unknown populations of trophoblastic stem-like cells (SLCs) that are resistant to the chemotherapeutic drug doxorubicin. We demonstrate that these populations express the stem cell markers NANOG and Sox2 and higher levels of OCT-4 (NANOG+/OCT-4high/SOX2+). Although chemoresistant, we show that the invasive capacity of these trophoblastic SLCs is significantly inhibited by doxorubicin treatment. To better characterise these populations, we also identified cellular pathways that are involved in SLCs-chemoresistance to doxorubicin. In summary, we provide evidence of the presence of NANOG+/OCT-4+/SOX2+ trophoblastic SLCs that are capable to contribute to the susceptibility to GTD and that may be involved in Chemoresistance associated with drug resistance and recurrence in high risk GTDs’ patients. We propose that targeting these populations could be therapeutically exploited for clinical benefit.Citation
Balahmar, R.M., et al. (2018). ‘Identification and characterisation of NANOG+/OCT-4high/SOX2+ doxorubicin-resistant stem-like cells from transformed trophoblastic cell lines’. Oncotarget, 9(6), pp. 7054-7065Publisher
Impact JournalsJournal
OncotargetDOI
10.18632/oncotarget.24151Additional Links
http://www.oncotarget.com/fulltext/24151Type
ArticleLanguage
enISSN
1949-2553ae974a485f413a2113503eed53cd6c53
10.18632/oncotarget.24151