An altered proteome in ovarian cancer stem-like cells: profiling of the mDivi-1 induced proteome and its clinical significance

Abstract

A three-dimensional (3D) spheroid culture mimics in vivo conditions and reproduces the tumor microenvironment, thus providing more physiological relevance to disease conditions. Mapping the proteome profile in 3D-cultured ovarian cancer (OC) spheroids helps identify novel and potential therapeutic targets in ovarian cancer stem cells. We used mass-spectrometry-based comparative proteome profiling for two-dimensional (2D)-cultured adherent and 3D-cultured OC spheroids and identified 94 upregulated and 54 downregulated proteins in 3D-cultured A2780 spheroids compared to 2D-cultured adherent A2780 cells. In SKOV-3 cells, we identified 127 upregulated proteins and 192 downregulated proteins in 3D-cultured spheroids compared to 2D-cultured adherent cells. The differentially expressed proteins were enriched in proteins regulating oxidative phosphorylation, the acetyl-CoA metabolic process, RNA polymerase core enzyme binding, and growth factor binding. In addition, we also mapped the proteome profile after the treatment with a mitochondrial fission inhibitor, mDivi-1, of 3D-cultured cells and defined the correlation between significantly upregulated and downregulated genes and their association with the progression-free survival of OC patients.