The development of novel therapeutic strategies for targeting ovarian cancer stem cells

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Emerging evidence suggests that human cancers arise from normal stem cells, and are composed of hierarchies of cells sustained by tumor-initiating cells(T-ICs), conceptually termed cancer stem cells(CSCs). Epithelial cell adhesion molecule(EpCAM) is a type I transmembrane glycoprotein that is expressed specifically in epithelial tissues and is overexpressed in some epithelial cancers. In normal tissues, EpCAM is expressed in several types of epithelial stem/progenitor cells and contributes to tissue development. On the other hand, a subpopulation of EpCAM-positive cells has been identified as CSCs in some human cancers. In the light of these considerations, we evaluated the EpCAM-positive cells for their stem cell properties in adult mouse ovary, and established the ovarian T-ICs by introduction of defined genetic elements in EpCAM-positive cells. EpCAM-positive cells possess the hallmarks of somatic stem cells and CSCs in this mouse model of ovarian tumorigenesis. Furthermore, our experimental mouse model facilitates further studies toward a comprehensive understanding of normal stem cells and CSCs in ovary. Ultimately, such studies will be imperative to define whether eradication of ovarian CSCs is critical for effective therapy.