Identification and characterisation of NANOG+/ OCT-4high/SOX2+ doxorubicin-resistant stem-like cells from transformed trophoblastic cell lines
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Reham M. Balahmar1, David J. Boocock2, Clare Coveney2, Sankalita Ray1, Jayakumar Vadakekolathu2, Tarik Regad2, Selman Ali1 and Shiva Sivasubramaniam1
1School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom
2The John van Geest Cancer Research Centre, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom
Shiva Sivasubramaniam, email: email@example.com
Keywords: trophoblast; stem-like cells (SLCs); doxorubicin; embryonic stem cells (ESCs); chemoresistance
Received: July 19, 2017 Accepted: January 02, 2018 Published: January 11, 2018
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 chemo-resistance 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 chemoresitance associated with drug resistance and recurrence in high risk GTDs’ patients. We propose that targeting these populations could be therapeutically exploited for clinical benefit.
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