Identification and characterisation of NANOG+/OCT-4high/SOX2+ doxorubicin-resistant stem-like cells from transformed trophoblastic cell lines
| Autor: | Reham M. Balahmar, Selman A. Ali, Clare Coveney, Shiva Sivasubramaniam, Tarik Regad, Sankalita Ray, David J. Boocock, Jayakumar Vadakekolathu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Homeobox protein NANOG business.industry Trophoblast Drug resistance Oct-4 Stem cell marker 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology SOX2 Cancer stem cell 030220 oncology & carcinogenesis embryonic structures Cancer research medicine Doxorubicin business reproductive and urinary physiology medicine.drug |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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