Identification and characterisation of NANOG+/OCT-4high/SOX2+ doxorubicin-resistant stem-like cells from transformed trophoblastic cell lines

Balahmar, RM, Boocock, DJ ORCID: https://orcid.org/0000-0002-7333-3549, Coveney, C ORCID: https://orcid.org/0000-0001-7047-6408, Ray, S, Vadakekolathu, J ORCID: https://orcid.org/0000-0002-2671-4285, Regad, T ORCID: https://orcid.org/0000-0003-4028-6368, Ali, S and Sivasubramaniam, S ORCID: https://orcid.org/0000-0001-7014-5000, 2018. Identification and characterisation of NANOG+/OCT-4high/SOX2+ doxorubicin-resistant stem-like cells from transformed trophoblastic cell lines. Oncotarget. ISSN 1949-2553

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Abstract

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.

Item Type:	Journal article
Publication Title:	Oncotarget
Creators:	Balahmar, R.M., Boocock, D.J., Coveney, C., Ray, S., Vadakekolathu, J., Regad, T., Ali, S. and Sivasubramaniam, S.
Publisher:	Impact Journals
Date:	11 January 2018
ISSN:	1949-2553
Identifiers:	Number Type 10.18632/oncotarget.24151 DOI
Rights:	© Balahmar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	17 Jan 2018 12:02
Last Modified:	04 Feb 2022 16:57
URI:	https://irep.ntu.ac.uk/id/eprint/32464

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