Ovarian cancer (OC) is the eight-most commonly occurring cancer in women. Carboplatin (CBP) and paclitaxel are usually the first therapy choice. The development of drug resistance is a major obstacle to successful therapy. Frequently, ovarian carcinoma cells undergo an epithelial-mesenchymal transition (EMT). There is an increasing need to find novel therapeutic targets and to understand the regulation of metastases.
Previously, we determined genes and miRNAs functionally confirmed to be involved either in acquired resistance, drug-induced metastasizing, or both. Preliminary data show that CBP-resistant cells in stem cell-supporting environment (Matrigel) form tube-like structures and are more invasive compared with parental cells. We hypothesize that the correlation between molecules with dual roles, and the invasive capacity of drug-resistant cells in a cancer stem cell-supporting environment exists. The first goal of this project is to establish OC cells with stable overexpression of molecules previously determined to be involved in drug resistance and drug-induced EMT and to confirm their role in drug resistance and/or metastasis in vivo as well. The second goal is to characterize tube-like structures formed in Matrigel by drug-resistant cells and possibly their regulation. The third goal is to explore the probable role of molecules of interest in the formation and regulation of tube-like structures and the invasive capacity of drug-resistant cells in Matrigel. The overall goal of this project is to understand molecular mechanisms behind tube-like structures formed by stem cells with acquired resistance to CBP and increased invasiveness and their correlation with previously determined molecules of interest. Data obtained will help us to understand better the complicity of acquired OC resistance and treatment-induced metastases. The gained knowledge will ensure the discussion of novel targets and approaches for ovarian cancer therapy.