Abstract 1496: Connecting the metallome with metabolism in ovarian cancer

Abstract

Abstract Ovarian cancer has historically been diagnosed late stage and lacks effective biomarkers for detection and prognosis. The deregulation of metabolism and signaling cascades inherent of cancer may contribute to aberrant levels of metal within cells. Biological processes essential for cell proliferation require metals for enzyme cofactors, signaling molecules, and structural components. Metallomics is the study of the comprehensive, dynamic metal profile within cells. The goal of our study was to characterize the ovarian cancer metallome at the level of whole cell and mitochondria in comparison to non-cancer. Additionally, cellular metabolism was analyzed to connect the mitochondrial (mito-)metallome to mitochondrial function. Ten human ovarian cancer cell lines were used for experiments: A2780, CAOV3, A2780/CIS, A2780/CP70, ES2, OVCAR3, OVCAR5, SKOV3, TOV112, and TOV21. Three non-cancer human ovarian cell lines of epithelial and fibroblast origin served as controls. Inductively coupled mass spectrometry (ICP-MS) was used to evaluate the metallome by measuring the following metals: calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), phosphorous (P), sulfur (S), selenium (Se), and zinc (Zn). An XF24 Seahorse analyzer was used to measure cellular metabolism and mitochondrial function in the ovarian cancer and non-cancer cell lines. Our results demonstrated that there was a distinct metal profile at the level of the whole cell and mitochondria in ovarian cancer cells compared to non-cancer ovarian cells. The whole cell ovarian cancer metallome consisted of increased Mg, P, and Cu, and decreased Fe, Mn, and Se in comparison to non-cancer. The cancer mito-metallome consisted of increased Mg, P, Cu, Zn, Se, and Ca. Referencing established literature of the known metals that serve as cofactors for mitochondrial proteins, the relationship between the mito-metallome and functional metabolic pathways was established. Changes in cellular metabolism were reflected by changes in the mito-metallome. Our study was the first to evaluate an extensive panel of metals simultaneously in the mitochondria and bridge the unique metal signature of ovarian cancer to cell metabolism. Future proteomics studies will be used to further validate the connection of metals to cellular function. Metallomics and the ovarian cancer cell metallome provide further understanding of how cancer deregulates the metallome and how metallomics may provide an avenue for identifying new cancer biomarkers and allow for effective targeting of cancer with chemotherapy. Citation Format: Eric D. Shide, Lauren Amable. Connecting the metallome with metabolism in 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 1496. doi:10.1158/1538-7445.AM2017-1496