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

新出现的证据表明，人类癌症起源于正常的干细胞，由肿瘤启动细胞（t - ic）维持的细胞层次组成，概念上称为癌症干细胞（CSCs）。上皮细胞粘附分子（Epithelial cell adhesion molecule, EpCAM）是一种I型跨膜糖蛋白，在上皮组织中特异性表达，在一些上皮癌中过表达。在正常组织中，EpCAM在几种类型的上皮干细胞/祖细胞中表达，并有助于组织发育。另一方面，epcam阳性细胞亚群已被确定为某些人类癌症中的CSCs。基于这些考虑，我们在成年小鼠卵巢中评估了epcam阳性细胞的干细胞特性，并通过在epcam阳性细胞中引入定义的遗传元件建立了卵巢t - ic。epcam阳性细胞在卵巢肿瘤发生小鼠模型中具有体细胞干细胞和CSCs的特征。此外，我们的实验小鼠模型有助于进一步研究卵巢正常干细胞和CSCs的全面认识。最终，这样的研究将是必要的，以确定根除卵巢csc是否对有效治疗至关重要。

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.