Characterization of SOX2, OCT4 and NANOG in Ovarian Cancer Tumor-Initiating Cells.
Mikella RobinsonSamuel F GilbertJennifer A WatersOmar Lujano-OlazabaJacqueline LaraLogan J AlexanderSamuel E GreenGregory A BurkeenOmid PatrusZinia SarwarRyne HolmbergChristine WangCarrie D HousePublished in: Cancers (2021)
The identification of tumor-initiating cells (TICs) has traditionally relied on surface markers including CD133, CD44, CD117, and the aldehyde dehydrogenase (ALDH) enzyme, which have diverse expression across samples. A more reliable indication of TICs may include the expression of embryonic transcription factors that support long-term self-renewal, multipotency, and quiescence. We hypothesize that SOX2, OCT4, and NANOG will be enriched in ovarian TICs and may indicate TICs with high relapse potential. We evaluated a panel of eight ovarian cancer cell lines grown in standard 2-D culture or in spheroid-enriching 3-D culture, and correlated expression with growth characteristics, TIC marker expression, and chemotherapy resistance. RNA-sequencing showed that cell cycle regulation pathways involving SOX2 were elevated in 3-D conditions. HGSOC lines had longer doubling-times, greater chemoresistance, and significantly increased expression of SOX2, OCT4, and NANOG in 3-D conditions. CD117+ or ALDH+/CD133+ cells had increased SOX2, OCT4, and NANOG expression. Limiting dilution in in vivo experiments implicated SOX2, but not OCT4 or NANOG, with early tumor-initiation. An analysis of patient data suggested a stronger role for SOX2, relative to OCT4 or NANOG, for tumor relapse potential. Overall, our findings suggest that SOX2 may be a more consistent indicator of ovarian TICs that contribute to tumor repopulation following chemotherapy. Future studies evaluating SOX2 in TIC biology will increase our understanding of the mechanisms that drive ovarian cancer relapse.
Keyphrases
- transcription factor
- poor prognosis
- stem cells
- optical coherence tomography
- cell cycle
- diabetic retinopathy
- cancer stem cells
- binding protein
- long non coding rna
- squamous cell carcinoma
- cell proliferation
- optic nerve
- cell cycle arrest
- obsessive compulsive disorder
- machine learning
- mass spectrometry
- case report
- risk assessment
- embryonic stem cells
- nk cells
- signaling pathway
- big data
- case control
- rectal cancer
- liquid chromatography
- simultaneous determination