Development and in vitro characterisation of an induced pluripotent stem cell model of ovarian cancer. (September 2021)

• Record Type: Journal Article
• Authors: Bindhya, S.; Sidhanth, C.; Krishnapriya, S.; Garg, Manoj; Ganesan, T.S.
• Is Part Of: International journal of biochemistry & cell biology. Volume 138(2021)
• Publication Date: 2021-09
• Subjects: HGSOC high grade serous ovarian cancer -- iPSCs induced pluripotent stem cells -- OCT4 octamer-binding transcription factor 4 -- SOX2 sex determining region Y -- KLF4 Krupple-like factor 4 -- SSEA stage-specific embryonic antigen -- TRA-1 tumour rejection antigen 1 -- GLIS1 Glis family zinc finger 1 -- hTERT human telomerase reverse transcriptase -- NOD non-obese diabetic -- SCID severe combined immunodeficiency -- SV 40 Simian Virus 40 -- CSC cancer stem cell -- FTE fallopian tube epithelial cells; iPSCs -- Stem cells -- Pathogenesis -- Ovarian cancer -- Drug resistance; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2021.106051
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Highlights: A first insight that both an ovarian cancer cell line and fallopian tube epithelial cells can be reprogrammed successfully. GLIS1 can successfully replace MYC as a transcription factor to generate induced pluripotent stem cells (iPSCs). iPSCs from PEO4 express putative novel surface markers and are resistant to drugs used in the treatment of ovarian cancer. Abstract: Ovarian cancer recurs despite advances in treatment and is due to drug resistance. The persistence of cancer stem cells (CSCs) is one of the causes. It has been challenging to maintain CSCs long term in culture from primary malignant cells. Reprogramming cancer cells into induced pluripotent stem cells (iPSCs) could be an approach to achieve this. An ovarian cancer cell line, PEO4, was initially reprogrammed into iPSCs using the classical four factors OCT 4, SOX2, KLF4 and MYC (OSKM) using lentivirus transduction. The PEO4-OSKM-cells had all the hallmarks of iPSCs. As MYC is oncogenic, we have replaced it with GLIS1 and show that PEO4 cells could be transformed into iPSCs. The transfection efficiency was two-fold better with OCT4-SOX2-KLF4-GLIS1 (OSKG) with larger colonies. Further, normal fallopian tube epithelial cells were also transformed using OSKG into iPSCs. iPSCs expressed CSCs markers such as CD133, EPHA1, ALDH1A1 and LGR5 prominently and were more resistant to cisplatin and taxol as compared to parental PEO4 cells. PEO4-OSKM-iPSCs cells formed more colonies in a clonogenic assay as compared to PEO4-OSKG-iPSCs and parental cells. These results provide a first insight that both an ovarian cancer cell line and fallopian tube epithelial cells can be reprogrammed and GLIS1 can successfully replace MYC as a transcription factor. This in vitro model is useful for future experiments to understand the characteristics of CSCs in the pathogenesis of ovarian cancer.