Background: Ovarian cancer is asymptomatic having no specific markers for detection at an early stage. Approximately 900 Australian women/year are diagnosed with stage lll/lV disease having survival rate of approximately 40% percent for five years. Recurrent peritoneal metastases development after standard chemotherapy treatment is a major clinical issue in the management of ovarian cancer. Hence, we need to identify molecules which can be manipulated in conjunction with chemotherapy treatment for better outcomes. Mitochondria are key organelles involved with metabolism of ovarian cancer cells. Genes encoding mitochondrial proteins have shown encouraging results as potential therapeutic targets for cancer. Our laboratory has recently identified novel expression of MAGMAS (mitochondria associated granulocyte macrophage colony stimulating factor signalling molecule) in ovarian tumours. Magmas has an important role in controlling oxidative damage. We aim to investigate role of MAGMAS in ovarian cancer progression, metastasis and chemoresistance associated recurrence while testing the effects of a Magmas-specific inhibitor (MI) on the expression of Magmas protein and drug resistant ovarian cancer stem cells (CSC). We will also evaluate the effect of MI on cellular metabolism (glycolysis, oxidative phosphorylation), reactive oxygen species production and activity of related enzymes such as cytochrome oxidase, glutathione peroxidase, superoxide dismutase and activity of mitochondrial complex I, II, III and IV in response to chemotherapy treatments.
Methods: Techniques employed are immunohistochemical and western blotting for investigating expression of Magmas protein on paraffin embedded ovarian tumour sections at different grades and clinical stage, and wide range of ovarian cancer cell lines with different metastatic potential. We will test the cytotoxic effects of MI in conjunction with paclitaxel on ovarian cancer cell lines and determine the overall effects on the expression of Magmas and CSC markers
Results: We demonstrate that Magmas has a significantly increased expression in ovarian tumour sections compared to benign tumours. We also report that Magmas expression is affected by chemotherapy treatments of ovarian cancer cell lines.
Conclusion:
Our results demonstrate novel Magmas expression-mediated alteration in the expression of cancer stem cell and chemoresistance markers. These findings implicate the chemoresistant role of Magmas in ovarian cancer.