Ovarian Epithelial Cancer Stem Cells

Abstract

The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies. Compared to the CSCs of other cancer types, the identification and study of EOC stem cells (EOCSCs) is rather difficult due to several major obstacles: the heterogeneity of tumors comprising EOCs, unknown cells of origin, and lack of knowledge considering the normal ovarian stem cells. This poses a major challenge for urgent development in this research field. This review summarizes and evaluates the current evidence for the existence of candidate normal ovarian epithelial stem cells as well as EOCSCs, emphasizing the requirement for a more definitive laboratory approach for the isolation, identification, and enrichment of EOCSCs. The present review also revisits the ongoing debate regarding other cells and tissues of origin of EOCs, and discusses early events in the pathogenesis of this disease. Finally, this review discusses the signaling pathways that are important regulators of candidate EOCSC maintenance and function, their potential role in the distinct pathogenesis of different EOC subtypes, as well as potential mechanisms and clinical relevance of EOCSC involvement in drug resistance.

VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients

“…The stem cell markers that were evaluated in this study are ALDH1 [13], CD24 [13], CD44 [14], CD133 [15], NOTCH3 [4], SOX2 [13], and CD117 [14]. All of these stem cell markers, except CD117, were more highly expressed in the SFCs than in the primary cancer cells (Fig.…”

“…CSCs have three main properties: (i) they express distinct surface markers; (ii) they are selectively endowed with tumorigenic capacity; and (iii) they sustain the growth of heterogeneous cancer tissues, therefore, displaying two of the functional hallmarks of stem cells, namely self-renewal and differentiation into multiple cell types [4][5][6][7]. CSCs also contribute to cancer recurrence through their resistance to anticancer drugs and their tumorigenic capacity, and many previous studies show that CSCs can resist chemoradiation therapy [6][7][8][9].…”

Human Epididymis Protein 4 (HE4) mRNA as a Prognostic Marker in Ovarian Tumors in Relation to RMI and CA125

“…Ovarian cancer represents a heterogeneous group of distinct tumors exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations and tumors behaviours (Conic et al, 2011). Goff (2012), reviewed that ovarian cancer had always been called ''The silent killer'' because symptoms are not thought to develop until advanced stages, when chances of cure were very poor.…”

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines

“…Comparison of stem cell markers, response to therapy, and best system for in vivo analysis needs to be conducted between different methods for generating/selection of CSCs. It has been suggested that there are different types of CSCs with different expression patterns of stem cell markers and different prognosis for patients [10][11][12] , thus further definition of what type of CSCs are generated by this protocol may help determine how they relate to human malignancy. Finally, in order to rigorously demonstrate that the CSCs isolated from this protocol are definitive CSCs, cells need to be injected into immunocompromised mice in a limiting dilution assay.…”