Abstract A66: The CD73+/CD24- subpopulation of ovarian cancer cells is enriched in cancer stem cells.

Abstract

Abstract Recent data suggest that drug resistance and/or disease recurrence in ovarian cancer (OC) are driven by a subpopulation of cells in human tumors with stem-like characteristics (cancer stem cells, CSCs). CSCs are defined as a small subpopulation of cells within the tumor bulk that possess the capacity, on one hand, to self-renew and, on the other hand, to give rise to all heterogeneous cancer cell lineages that compose the tumor of origin. The CSC hypothesis provides an attractive cellular mechanism to explain the therapeutic refractoriness, dormant behavior, and relapse of OC. Our study aims at assessing ovarian cancer stem cells (OCSC) as causal players in OC etiology and progression and at defining their molecular and functional traits. Specifically, we are pursuing these objectives through the accomplishment of the following milestones: 1) collection of normal and pathological samples; 2) identification of OCSC based on functional properties; 3) comparison of gene expression profiles between cancer stem cells and their normal counterpart; 4) characterization of novel genes/pathways involved in OCSC function (clonogenicity, tumorigenicity, quiescence, chemoresistance, etc.). This workflow has been applied to surgical samples of OC as well as to normal ovarian surface epithelium (OSE) and fallopian tube epithelium (FTE), namely the tissues of origin of OC. OCSC have been derived from primary cultures exploiting their ability to resist anoikis and form monoclonal spheroids when cultured under nonadherent conditions. The transcriptome of OC-derived spheroids was compared with that of their normal counterparts, yielding a set of differentially expressed genes. Among these, for the initial characterization we have selected two cell surface markers CD73, upregulated in spheroids, and CD24, downregulated in spheroids. The CD73+/CD24- subpopulation was enriched in sphere-forming cells and, most importantly, exhibited higher tumorigenic capacity when xenografted in immunocompromised mice. Thus, by utilizing clinically relevant samples we have characterized the transcriptome of OCSC and of their normal counterparts. Furthermore, we found that the CD73+/CD24- phenotype in ovarian cancer is associated to CSC-like traits. On one hand, our approach revealed novel OCSC biomarkers that can be exploited for imaging and purification purposes. On the other hand, we have identified potential therapeutic targets, such as CD73, that might set the stage for innovative treatments aimed at the eradication of OC through the elimination of OCSC. Citation Format: Michela Lupia, Giovanni Bertalot, Pier Paolo Di Fiore, Nicoletta Colombo, Fabrizio Bianchi, Ugo Cavallaro. The CD73+/CD24- subpopulation of ovarian cancer cells is enriched in cancer stem cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A66.