Abstract 2359: Regulation of cytoskeleton organization by sphingosine in a mouse cell model of ovarian cancer progression

Abstract

Abstract Ovarian cancer is the fifth leading cause of cancer deaths among women mainly because of late detection of the disease due the lack of symptoms and reliable biomarkers. Approximately 90% of ovarian cancers are derived from the surface epithelium of the ovary. To further investigate the events that lead to progression of epithelial ovarian cancer, we previously developed a cell model of ovarian cancer. Mouse ovarian surface epithelial (MOSE) cells that have undergone spontaneous transformation in cell culture were categorized into distinct morphological and phenotypical stages based on passage history: early passage cells (MOSE-E) represent a pre-neoplastic, non-tumorigenic phenotype whereas late passage cells (MOSE-L) exhibit a highly aggressive malignant phenotype both in vitro and in vivo. In depth studies of genetic changes during MOSE cell progression in our labs have identified the cytoskeleton and its regulatory genes as critical early progression events. These changes in gene expression led to an increasingly dysregulated cytoskeleton which may affect the intracellular localization of signaling intermediates, and, thereby, important downstream signaling events involved in cancer progression. Sphingosine (SO), a bioactive metabolite of complex sphingolipids, has been shown to have chemopreventive activity against cancer, including cancer of the colon, breast and ovarian. In the present study, we have investigated the hypothesis that SO prevents or reverses the observed aberrant cytoskeleton organization, and thereby affects the cells metastatic potential. In MOSE-L cells, SO treatment did not significantly influence the gene expression or protein levels of several cytoskeleton components or regulatory proteins. However, immunostaining of SO-treated MOSE-L cells revealed a reversal of the aberrant cytoskeleton organization and mislocalization of regulatory proteins, many of which are associated with cell migration. This corresponds to observations that SO reduces cell motility in MOSE cells. Our data indicates that cytoskeleton re-organization induced by exogenous SO treatment may be involved in the regulation of signaling pathways that reduce proliferation, migration and invasion of the MOSE cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2359. doi:10.1158/1538-7445.AM2011-2359