Abstract
Abstract We have reported a tumor suppressor effect of SPARC in ovarian cancer as both host and tumor SPARC are implicated in anti-proliferative, anti-adhesive effects as well as normalization of the peritoneal tumor microenvironment. Herein, we extend our studies using a syngeneic model of peritoneal ovarian carcinomatosis to gain comprehensive insight on the effect of SPARC on metabolic programming of the ovarian cancer ecosystem. We performed comprehensive metabolomic and transcriptomic profiling of micro-dissected ID8 omental tumors that developed after intra-peritoneal injection in SP-/- and SP+/+ mice. Integrated analysis revealed that the accelerated growth of ID8 tumors in SP-/- mice was associated with metabolic programming of cancer cells with up-regulation of the genes involved in glycolysis, fatty acid oxidation, and oxidative phosphorylation. Tumors also exhibited perturbed redox homeostasis, as well as mitochondrial and ribosomal biogenesis. Comparative analysis of the syngeneic tumors with human high grade serous ovarian cancer (HGSC) revealed upregulation of the same genes involved in metabolic programming with inverse correlation with SPARC transcript expression, implying a role of stromal-SPARC in the metabolic programming of HGSC. Bio-energetic studies revealed that SPARC inhibits basal glycolysis, glycolytic reserve, oxygen consumption rate and mitochondrial ATP synthesis. To the best of our knowledge this is the first study that characterizes the metabolic programming of the ovarian cancer ecosystem by host-SPARC. Citation Format: Christine Naczki, Bincy John, Chirayu Patel, Ashlyn Lafferty, Alia Ghoneum, Hesham Afify, Amanda Davis, Guangxu Jin, Neveen Said. Integrated molecular analysis reveals novel SPARC-regulated metabolic programming in 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 1448.
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