LAUSR

Ovarian cancer is the fifth leading cause of cancer death in women and the most lethal gynecologic malignancy. High-grade serous ovarian carcinoma (HGSC) originates mainly from the fallopian tube epithelium, and is characterized by TP53 mutation identified in all HGSCs as well as the fallopian tubal precursor of serous tubal intraepithelial carcinomas (STICs). The loss of a functional TP53 is an early event in the malignant transformation of fallopian tube epithelium. We have established 4 primary cell cultures of normal fallopian tube epithelial (FTE) cells, and further generated immortalized FTE cells using SV40 large plus small T antigens (FTE-TAg) to disrupt TP53 function. This model mimics the primary lesions of ovarian cancer and is suitable to identify biomarkers and molecular targets of ovarian cancer. Therefore, we compared the secretomes of primary FTE cells with that of their parental isogenic pairs FTE-TAg cells using mass spectrometry analysis. We identified 813 proteins, 228 of which were differentially expressed. Ingenuity Pathway Analysis (IPA) core analysis revealed glycolysis as a major canonical pathway. Overexpression of key enzymes of glycolytic pathway was confirmed by IHC in human STIC lesions. Molecular mechanisms of glycolysis regulation in premalignant lesion of ovarian cancer were determined. Role of glycolysis in the establishment of premalignant ovarian cancer microenvironment (PME) was characterized. Prevention approaches targeting glycolysis were tested in transgenic animal model of ovarian cancer. Citation Format: Anna E. Lokshin, Mounia Alaoui El Azher, Liudmila Velikokhatnaya, Denise Prosser. Elevated glycolysis in pre-malignant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5142.