J Cancer 2018; 9(6):1006-1016. doi:10.7150/jca.22932

Research Paper

Switch of the ovarian cancer cell to a calcifying phenotype in the calcification of ovarian cancer

Jirui Wen1,2*, Zhiwei Zhao2*, Liwei Huang3, Liang Li2, Jiman Li4, Ye Zeng2, Jiang Wu2, Yali Miao1✉

1. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, P.R. China
2. West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China
3. West China School of Stomatology Medicine, Sichuan University, Chengdu, China
4. Pathology Department, Sichuan Cancer Hospital, Chengdu, China
*The first two authors made an equal contribution to the paper.

Abstract

Objective: The main aim of this study was to study swith of the ovarian cancer cell to a calcifying phenotype in the formation of calcification in ovarian cancer, and to offer some help for ovarian cancer's diagnosis and differentiation therapy.

Methods: The mineralization of ovarian cancer cell lines SKOV3 was induced via calcification medium for 21 d in vitro. Alizarin red staining, von kossa staining, calcein fluorescence staining and ALP activity detection were used to identify mineralization in calcification model of ovarian cancer. Also, the changes of ultrastructure and the mineralization biomarkers after the induction of calcification medium were investigated by transmission electron microscopy and western blot, respectively. The SKOV3 cells migration behavior after the induction of calcification medium was evaluated by using transwell assay and scratch wound. Finally, mineralization biomarkers were verified in 40 cases of calcified ovarian cancer specimens and matched 40 non-calcified ovarian cancer tissues.

Results: Classical calcium salt detection methods confirmed that the culture of SKOV3 cells in calcification medium was an appropriate ovarian cancer calcification model in vitro. Transmission electron microscopy and western blot revealed respectively the presence of cells with morphological characteristics of osteoblasts and the upregulation of mineralization biomarkers expression in treatment group. Transwell assay and scratch wound showed the decreased SKOV3 cell migration in treatment group. In specimens, the calcification occurred predominantly in well-differentiated carcinomas and the expression of the BMP2 and OPN elevated in calcified group.

Conclusion: Our study showed that the switch of the ovarian cancer cell to a calcifying phenotype in the formation of calcification in ovarian cancer. The calcified phenotypic transformation may inform the new prospective in ovarian cancer therapy.

Keywords: ovarian cancer, calcification, migration, phenotypic transformation, differentiation therapy

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How to cite this article:
Wen J, Zhao Z, Huang L, Li L, Li J, Zeng Y, Wu J, Miao Y. Switch of the ovarian cancer cell to a calcifying phenotype in the calcification of ovarian cancer. J Cancer 2018; 9(6):1006-1016. doi:10.7150/jca.22932. Available from http://www.jcancer.org/v09p1006.htm