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Abstract
Abstract Epithelial Ovarian Cancer (OC) is one of the leading causes of death for women, and no significant therapeutic progress has been made in the last decades. Recent data suggest that one of the mechanisms accounting for resistant and/or relapsing disease is 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 the disease. 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 profile. Specifically, we are pursuing the following objectives through the accomplishment of these 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 is being applied to a series of fresh 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. Thus, we obtained a collection of primary cells that recapitulate many traits of the original tissue both in vitro and in vivo. The gene expression profiles of sphere-forming SC has been compared to that of adherent, parental cells, aimed at identifying stemness-associated genes. This screening has been extended to OC, OSE, and FTE, resulting in a set of genes that are differentially expressed in OCSC as compared to their normal counterparts. A subset of such genes has been selected for the subsequent validation, both as OCSC biomarkers that could have clinical applications and as drivers in the biological and pathogenic function of OCSC. Our study might set the stage for innovative therapeutic approaches aimed at the selective elimination of OCSC, thus preventing tumor recurrence and chemoresistance, namely the two main causes of ovarian cancer lethality. Citation Format: Michela Lupia, Giovanni Bertalot, Nicoletta Colombo, Stefano Confalonieri, Pier Paolo Di Fiore, Ugo Cavallaro. Molecular and functional characterization of ovarian cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1414. doi:10.1158/1538-7445.AM2015-1414
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