J Cancer 2020; 11(2):272-283. doi:10.7150/jca.34965

Research Paper

CD105 overexpression mediates drug-resistance in choriocarcinoma cells through BMP9/Smad pathway

Xiaoyu Wang1, Liju Zong1, Wenze Wang2, Junjun Yang1✉, Yang Xiang1✉

1. Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Dongcheng District, Beijing 100730, China.
2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Dongcheng District, Beijing 100730, China.

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Citation:
Wang X, Zong L, Wang W, Yang J, Xiang Y. CD105 overexpression mediates drug-resistance in choriocarcinoma cells through BMP9/Smad pathway. J Cancer 2020; 11(2):272-283. doi:10.7150/jca.34965. Available from https://www.jcancer.org/v11p0272.htm

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Abstract

Background: CD105 (endoglin, ENG) is a membranous protein that is overexpressed in tumor-associated endothelial cells and some actual tumor cells and is associated with poor prognosis. However, the association between CD105 and response to chemoresistance in choriocarcinoma cells has not been clearly defined. The present study aimed to investigate the effects of targeting CD105 in drug-resistant choriocarcinoma.

Methods: CD105 expression was evaluated in drug-resistant and parental choriocarcinoma cells by qRT-PCR, western blotting, and immunofluorescence. CD105 overexpressing and knockdown cells were established by lentiviral transfection. CCK8, transwell, and flow cytometric assays were used to measure changes in drug-sensitivity, invasion, migration, and apoptosis. Drug-sensitivity and Smad1/5/8, Smad2, and Smad3 expression were also detected after BMP9 treatment. Immunohistochemical staining for CD105 and BMP9 was performed on choriocarcinoma tissues and the relationships between clinical and pathological characteristics were analysed.

Results: Data demonstrated that CD105 overexpression could decrease drug sensitivity, promote invasion and migration, and inhibit apoptosis in choriocarcinoma cells, and this protein was confirmed to mediate drug resistance through the BMP9/Smad pathway. Further experiments showed that the expression of CD105 and BMP9 was consistent in choriocarcinoma tissues and significantly associated with disease recurrence.

Conclusions: This study provides evidence suggesting that CD105 is critical for the development of drug-resistance in choriocarcinoma and might serve as a therapeutic target for reversing chemoresistance in choriocarcinoma patients.

Keywords: BMP9/Smad pathway, CD105, chemoresistance, choriocarcinoma