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

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In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells
08:21

In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells

Published on: March 16, 2017

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Reham M Balahmar1, David J Boocock2, Clare Coveney2

  • 1School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom.

Oncotarget
|February 23, 2018
PubMed

Insights

Researchers discovered novel trophoblastic stem-like cells (SLCs) resistant to chemotherapy in gestational trophoblastic diseases (GTD). Targeting these NANOG+/OCT-4high/SOX2+ cells may improve treatment for high-risk GTD patients, addressing drug resistance and recurrence.

Area of Science:

  • Reproductive Medicine
  • Oncology
  • Stem Cell Biology

Background:

  • Gestational trophoblastic diseases (GTD) are treated with surgery, radiotherapy, and chemotherapy.
  • Drug resistance and toxicity are significant challenges, particularly in high-risk patients.
  • Cancer stem cells are implicated in tumor recurrence and chemoresistance.

Purpose of the Study:

  • To identify and characterize novel trophoblastic stem-like cells (SLCs) in GTD.
  • To investigate the chemoresistance of these SLCs to doxorubicin.
  • To explore potential therapeutic targets for high-risk GTD.

Main Methods:

  • Identification of trophoblastic stem-like cells (SLCs) expressing stem cell markers NANOG, OCT-4, and Sox2.
  • Assessment of doxorubicin resistance and its effect on the invasive capacity of SLCs.
  • Analysis of cellular pathways involved in SLC chemoresistance.

Main Results:

  • Previously unknown trophoblastic SLCs (NANOG+/OCT-4high/SOX2+) were identified.
  • These SLCs exhibit resistance to the chemotherapeutic drug doxorubicin.
  • Doxorubicin treatment significantly inhibited the invasive capacity of these chemoresistant SLCs.
  • Cellular pathways contributing to doxorubicin resistance were identified.

Conclusions:

  • The study provides evidence for NANOG+/OCT-4high/SOX2+ trophoblastic SLCs in GTD.
  • These SLCs may contribute to GTD susceptibility and chemoresistance, leading to drug resistance and recurrence in high-risk patients.
  • Targeting these specific trophoblastic SLC populations presents a potential therapeutic strategy for clinical benefit.
Keywords:
chemoresistancedoxorubicinembryonic stem cells (ESCs)stem-like cells (SLCs)trophoblast

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