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Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors
Published on: March 1, 2020
SOX2 is required to maintain cancer stem cells in ovarian cancer
Yiping Wen1, Yaya Hou1, Zaiju Huang1
1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Ovarian cancer cells can form spheroids under serum-free suspension culture conditions. The spheroids, which are enriched in cancer stem cells, can result in tumor dissemination and relapse. To identify new targetable molecules in ovarian cancer spheroids, we investigated the differential expression of genes in spheroids compared with that under monolayer culture conditions by qPCR microarray. We identified that SOX2 is overexpressed in spheroids. We then proved that SOX2 expression was increased in successive spheroid generations. Besides, knockdown of SOX2 expression in SKOV3 or HO8910 ovarian cancer spheroid cells decreased spheroid formation, cell proliferation, cell migration, resistance to Cisplatin treatment, tumorigenicity, and the expression of stemness-related genes and epithelial to mesenchymal transition-related genes, whereas overexpression of SOX2 in SKOV3 or HO8910 ovarian cancer cells showed the opposite effects. In addition, we found that SOX2 expression was closely associated with chemo-resistance and poor prognosis in EOC patients. These results strongly suggest that SOX2 is required to maintain cancer stem cells in ovarian cancer. Targeting SOX2 in ovarian cancer may be therapeutically beneficial.
Insights
SOX2 is overexpressed in ovarian cancer spheroids, which are enriched in cancer stem cells. Targeting SOX2 may offer a therapeutic strategy for ovarian cancer by inhibiting cancer stem cell maintenance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Ovarian cancer spheroids, enriched in cancer stem cells (CSCs), contribute to tumor dissemination and relapse.
- Identifying novel therapeutic targets in CSC-enriched ovarian cancer spheroids is crucial.
Purpose of the Study:
- To identify targetable molecules overexpressed in ovarian cancer spheroids.
- To investigate the role of SOX2 in maintaining ovarian cancer stemness and its therapeutic potential.
Main Methods:
- Quantitative real-time PCR (qPCR) microarray to analyze gene expression differences between spheroid and monolayer cultures.
- SOX2 knockdown and overexpression experiments in ovarian cancer cell lines (SKOV3, HO8910).
- Assessment of spheroid formation, cell proliferation, migration, chemoresistance, and tumorigenicity.
- Correlation analysis of SOX2 expression with clinical data from epithelial ovarian cancer (EOC) patients.
Main Results:
- SOX2 was identified as significantly overexpressed in ovarian cancer spheroids compared to monolayer cultures.
- SOX2 expression increased with successive spheroid generations.
- SOX2 knockdown reduced spheroid formation, proliferation, migration, chemoresistance, and tumorigenicity, while decreasing stemness and epithelial-to-mesenchymal transition (EMT) markers.
- SOX2 overexpression yielded opposite effects.
- Elevated SOX2 expression correlated with chemoresistance and poor prognosis in EOC patients.
Conclusions:
- SOX2 is essential for maintaining cancer stem cell properties in ovarian cancer.
- Targeting SOX2 presents a promising therapeutic avenue for ovarian cancer treatment.
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