Investigating the role of microenvironment and matrix stiffness in ovarian cancer development

The mechanical properties of the ECM play an important role in cell differentiation and growth. However, it remains unclear how OCCs respond to changes in the mechanical properties (stiffness/rigidity) of the microenvironment. In this study we used 6-well stiffness plates and a polyacrylamide-based hydrogel to mimic the varying stiffness in the human body. We cultured OCCs on these substrates and investigated alterations to morphology, cell death, and cell cycle. We found that with increased stiffness, actin fibres were more defined, and cells were more elongated. In addition, we observed a decrease in cell death with increased stiffness in COV362 cells and no significant changes in OVCAR3 cells. Additionally, when we treated cells with paclitaxel, there was an increase in cell death. We also analysed cell cycle phases and found that cell cycle progression was interrupted as the majority of the cells were present at the G1 phase. Protein expression with changing mechanical stimuli was analysed and we found a number of upregulated and downregulated proteins. Proteins involved in DNA repair, cell cycle, and cell death were detected as upregulated in the nucleus. Likewise, the cytoplasm expressed downregulated proteins involved in apoptosis, wound healing, and actin- cytoskeletal reorganisation. These observations suggests that the mechanical properties of the matrix environment plays a significant role in regulating major cellular processes. Furthermore, proteins altered due to changing stiffness can pave the way for the development of novel therapeutic targets.