The identification of the biological characteristics of human ovarian cancer stem cells

H.C. Yan, L.S. Fang, J. Xu, Y.Y. Qiu, X.M. Lin, H.X. Huang, Q.Y. Han

Department of Obstetrics and Gynecology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China. 1015058194@qq.com

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• Oncology

OBJECTIVE: Identifying the biological characteristics of previously screened ovarian cancer cell line HO8910-derived stem cells.

MATERIALS AND METHODS: The pre-screening of ovarian cancer cell line HO8910-derived stem cells were subcultured (HO8910 cells were used as a control group) in serum-free medium. Firstly, the capacities of forming spheroids and self-renewal were observed. Then ovarian cancer stem cells (CSCs) were seeded in medium containing serum and cultured to observe the changes in their ability to differentiate. The stem cell-specific markers were also tested. Secondly, we tested the sensitivity of stem cells to cisplatin, doxorubicin, and mitoxantrone using drug susceptibility test. Finally, we inoculated the ovarian CSCs after passaging from culturing in serum-free media to NOD/SCID (non-obese diabetic/severe combined immunodeficient mice) mice in order to observe the tumorigenicity in vivo.

RESULTS: Ovarian CSCs cultured in serum-free medium are capable of forming stable passaged cells spheres and have strong ability of self-renewal and differentiation. Under the condition of serum-free medium culture, the expression levels of CDl33+, CD117+, ABCG2, Nanog, Oct4, and BCRP in ovarian cancer stem cell are significantly higher than the counterparts in HO8910 cells. With the increase of the ability of differentiation, the stem cell marker expression levels reduced. While the differentiation, potential marker-E-cadherin expression levels were significantly lower than the control group. With the increase of the ability to differentiate, E-cadherin expression level was increased. Ovarian CSCs have significant resistance to cisplatin, doxorubicin, and mitoxantrone. NOD/SCID nude mice experiments showed that ovarian cancer stem cell tumorigenicity was significantly higher than control cells and has a continuous tumorigenicity.

CONCLUSIONS: Comparing ovarian CSCs derived from HO8910 to HO8910 cells, the stem cells have significantly enhanced abilities of self-renewal, differentiation, in vivo tumorigenicity, highly expressed stem cell genes, and multidrug resistance.

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