High-throughput 3-dimensional culture of epithelial ovarian cancer cells as preclinical model of disease
Victoria Heredia-Soto 1 2 , Andrés Redondo 3 4 5 , Alberto Berjón 1 6 , María Miguel-Martín 1 , Esther Díaz 4 , Roberto Crespo 4 , Alicia Hernández 7 , Laura Yébenes 1 6 , Alejandro Gallego 3 , Jaime Feliu 2 3 4 5 8 , David Hardisson 1 5 6 9 , Marta Mendiola 1 2 9
Background: Recent reports have identified distinct genomic patterns in ovarian carcinoma, including proliferative and mesenchymal-like groups, with worse outcome. The exact mechanisms driving the onset and progression of these tumors are still poorly understood. Additionally, researchers are concerned about the correct subtype stratification of the available cell line models, and the exploration of alternatives to monolayer culture. Identification of biomarkers to stratify cell lines, characterization of important processes as epithelial-mesenchymal transition (EMT), and the use of three-dimensional (3D) cultures as alternative models could be useful for cell line classification.
Methods and results: In this work, we present a descriptive analysis of 16 commonly used ovarian cancer cell lines. We have studied their morphology in 2- and 3D culture, and their response to cisplatin, observing in the majority of them an increased resistance in 3D. We have also performed an immunohistochemical analysis for proliferation marker Ki-67, and EMT related markers to establish phenotypes. Epithelial cells tend to show higher proliferative rates, and mesenchymal cells show an increase in EMT related markers, especially when cultured in 3D conditions.
Conclusions: We have stated the complex heterogeneity of ovarian cancer models, resembling primary tumors, agreeing with the argument that the cell line model for in vitro experiments must be carefully chosen. Our results also support that tridimensional culture could be a very helpful alternative in ovarian cancer research. Regarding EMT, a very important process for the development of this disease, some related biomarkers might be further characterized for their role in this disease development.
CITATION Oncotarget. 2018 Apr 24;9(31):21893-21903. doi: 10.18632/oncotarget.25098