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- W2067990028 abstract "The formation of cellular spheroids is considered to be an important step in the metastatic progression of ovarian cancer. These clusters of tumor cells are characterized by an enhanced survival within the peritoneal cavity, the ability to attach at secondary metastatic sites within the cavity and associated with increased chemoresistance. High expression of mitochondrial superoxide dismutase (Sod2), which regulates mitochondrial redox balance, has been observed in metastatic ovarian cancer, specifically ovarian clear cell carcinomas (CCC), and in vitro, following spheroid formation. To assess the role of Sod2 in spheroid formation and ovarian cancer metastasis we utilized siRNA knock-down to decrease Sod2 expression in Ovcar3 and the CCC cell line ES-2. Surprisingly, under normal culture conditions, decreasing Sod2 levels had little effect on proliferation and spheroid formation. To elucidate the role of Sod2 on ovarian cancer mitochondrial function an extracellular flux metabolic analyzer (Seahorse Bioscience) was utilized to measure rates of cellular respiration. While the basal oxygen consumption rate remained unchanged, a decrease in Sod2 expression resulted in a concomitant decrease in respiratory reserve capacity. This reserve capacity is an important determinant of a cell9s ability to increase metabolic rate under stress conditions. Given that ovarian cancer spheroids are exposed to the hypoxic environment of the peritoneal cavity, the role of Sod2 on ovarian cancer spheroid formation was assessed under low oxygen (1%) conditions. Hypoxia increased the clonogenicity and spheroid size of control cells, which was significantly abrogated following Sod2 knock-down. These data suggest that Sod2 confers a survival advantage to ovarian cancer spheroids under stress conditions by maintaining an adequate mitochondrial respiratory reserve. Manipulating mitochondrial function and redox balance by effectively targeting mitochondrial antioxidant enzymes may enhance chemosensitivity and allow for novel therapeutic strategies against ovarian cancer. Citation Format: Usawadee Dier, Larissa Uusitalo, Corinne Giroux, Nadine Hempel. Mitochondrial superoxide dismutase (Sod2) confers a survival advantage to ovarian cancer cells under stress conditions by enhancing mitochondrial respiratory reserve capacity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B40." @default.
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- W2067990028 date "2013-02-01" @default.
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- W2067990028 title "Abstract B40: Mitochondrial superoxide dismutase (Sod2) confers a survival advantage to ovarian cancer cells under stress conditions by enhancing mitochondrial respiratory reserve capacity" @default.
- W2067990028 doi "https://doi.org/10.1158/1538-7445.tim2013-b40" @default.
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