Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC)

Abstract

Epithelial ovarian cancer (EOC) cell lines are useful tools for the molecular and biological characterization of ovarian cancer. The use of an in vitro multidimensional (3-D) culture model recapitulates some of the growth conditions encountered by tumor cells in vivo. Here we describe a molecular comparison of spheroid based 3D EOC models versus monolayer cultures and xenografts using cell lines from malignant ovarian tumors (TOV-21G and TOV-112D) and ascites (OV-90) previously established and characterized in our laboratory. Gene expression analyses of the three models were performed using the Affymetrix HG-U133A high density DNA array. Cluster analysis identified a set of genes that stratified expression profiles from the EOC cell lines grown as spheroids and xenografts from that of monolayer cultures. The gene expression analysis results were validated by Q-PCR analyses on an independent set of RNAs. Differential expression observed for the S100A6 gene between the monolayer, spheroid cultures and xenografts was confirmed at the protein level by immunohistochemistry. The analysis was extended to various ovarian tumor tissues using an EOC tissue array. This result represents an example of a gene that, if studied in vitro, is more representative of the in vivo disease in a 3D model rather than the monolayer culture. Identification of genes in spheroid models that mimic the in vivo tumor gene expression patterns may allow a better understanding of the community effect observed in human disease that is determined by direct or indirect interactions of cells with their environment or other surrounding cells.