Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation

被引：6

作者：

de Lima, Aline Brito ^{[1
,2
]}

Silva, Luciana Maria ^{[1
]}

Goncales, Nikole Gontijo ^{[1
]}

Santos Carvalho, Maria Raquel ^{[2
]}

da Silva Filho, Agnaldo Lopes ^{[3
]}

Braga, Leticia da Conceicao ^{[1
,3
]}

机构：

[1] Fundacao Ezequiel Dias, Serv Biol Celular, Belo Horizonte, MG, Brazil

[2] Univ Fed Minas Gerais, Lab Genet Humana & Med, Belo Horizonte, MG, Brazil

[3] Univ Fed Minas Gerais, Dept Ginecol & Obstet, Belo Horizonte, MG, Brazil

来源：

CANCER MICROENVIRONMENT | 2018年 / 11卷 / 01期

关键词：

Epithelial ovarian cancer; Cancer stem cells; microRNAs; Apoptosis; In vitro cultivation-models; STEM-CELLS; BREAST-CANCER; GENE; DYSREGULATION; METHYLATION; AUTOPHAGY; MICRORNAS; PATHWAYS; MIR-26; TUMORS;

D O I：

10.1007/s12307-017-0203-z

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and SKOV-3 were cultured in monolayer and tumorspheres. Genetic profiles of cell lines were obtained using COSMIC database. CD24/CD44/CD146/CD177 and ALDH1 markers were evaluated in cell lines and tumorspheres-derived by flow cytometry. Eleven miRNAs were selected by in silico analysis for qPCR analysis. According to COSMIC, TOV-21G and SKOV-3 have eight and nine cancer-related mutations, respectively. TOV-21G showed a CD44(+/high)/CD24(-/low)/CD117(-/low)/CD146(-/low)/ALDH1(low) profile in both culture models; thus, no significant difference between cultivation models was identified. SKOV-3 showed a CD44(+/high)/CD24(+/high)/ CD117(-/low)/CD146(-/low)/ALDH1(low) profile in both culture models, although the tumorsphere model showed a significant increase in CD24(+/high) subpopulation (ovarian CSC-like). Among eleven miRNAs, we observed differences in miRNA expression between culture models. MiR-26a was overexpressed in TOV-21G tumorspheres, albeit downregulated in SKOV-3 tumorspheres. MiR-125b-5p, miR-17-5p and miR-221 was downregulated in tumorsphere model in both cell lines. Given that tumorsphere-derived SKOV-3 had a higher ratio of CD24(+/high) cells, we suggest that miR-26a, miR-125b-5p, miR-17-5p and miR-221 downregulation could be related to poor EOC prognosis.

引用

页码：85 / 92

页数：8