Abstract 2505: High-resolution MRS characterization of malignant ascites in two models of ovarian cancer
Authors: Bharti Santosh , Wildes Flonne , Hung Chien-Fu , Wu TC , Bhujwalla Zaver , Penet Marie-France 
Published: July 2017

Build-up of malignant ascites occurs in more than one third of ovarian cancer patients and significantly contributes to poor quality of life and mortality. Advances in understanding malignant ascites formation and finding new therapeutic options are urgently needed. High-resolution 1H MRS has been described as extremely useful in detecting endogenous metabolites to diagnose cancer, by providing a detailed overview of metabolic pathways in a single measurement. In the present study, we are using two ovarian cancer cell lines, the murine ID8-VEGF-Defb29 cell line and the human OVCAR3 cell line. Implanted orthotopically, these two ovarian cancer models are characterized by different profile of ascites formation. The mouse cell line ID8-VEGF-Defb29 induces large volumes of ascites, often more than 10 mL, while the human OVCAR3 cell line induces ascites less frequently and at smaller volumes, usually less than 0.2 mL. We applied high-resolution 1H MRS to compare the metabolic composition of both ascitic fluids. To better understand the differences observed, we characterized the metabolism of these ovarian cancer cells in culture by analyzing cell lysates and conditioned culture media with 1H MRS to advance our understanding of cancer cell metabolic reprogramming in malignant ascites formation and the role of the tumor microenvironment in ascites formation and composition. The two tumor models used in this study induced different ascitic profiles. While OVCAR3 tumor bearing mice developed small viscous volume of ascites, ID8-VEGF-Defb29 induced higher volumes. ID8-VEGF-Defb29 ascitic fluids were characterized by higher levels of glutamine, glucose, poly-unsaturated fatty acids and pyruvate compared to the OVCAR3 fluids, while all the other metabolites, including glutamate, lactate, myo-inositol, choline and acetate, were lower. To determine if the differences observed in the ascitic fluids were only due to a different metabolism of the cancer cells, we investigated their metabolism in vitro. We analyzed the metabolites present in the conditioned cell culture media, and in the cells, and observed differences in OVCAR3 and ID8-VEGF-Defb29 cells metabolism in vitro, without replicating the differences observed in vitro. A Venn diagram of the different metabolites present in the cells, media and ascites showed differences in the metabolites present in those 3 compartments, and highlighted the ones in common. Beta-hydroxybutyrate, lipids, maleic and citrate were found in both ascites, and not in the cells or media. Ascites MRS derived biomarkers could help in ovarian cancer diagnosis, and enhance our understanding of the biochemical and metabolic changes associated with ovarian cancer, and with ascites formation.

Supported by Tina’s Wish Foundation, NIH P50CA013175 and P30CA06973.

Citation Format: Santosh Bharti, Flonne Wildes, Chien-Fu Hung, TC Wu, Zaver Bhujwalla, Marie-France Penet. High-resolution MRS characterization of malignant ascites in two models of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2505. doi:10.1158/1538-7445.AM2017-2505