Stem cells in endometrium and endometrial cancer: accumulating evidence and unresolved questions

Abstract

The human endometrium undergoes cyclical process of regeneration, growing from less than 1mm in thickness just after menstruation to 7-8 mm in only 2 weeks, which is accompanied by functional differentiation, followed by shedding of the functional layer. Since endometrium can fully regenerate even after complete physical shedding, there may be a cell population residing in the basal layer that can continue to provide daughter cells with high proliferative potential. Such a cell population is assumed to have stem cell characteristics. This review article aims to introduce evidence of the presence of stem cells not only in normal endometrium but also in endometrial cancer and discusses their roles in physiological regeneration and in carcinogenesis of the endometrium. Accumulating evidence revealed that there are rare individual cells that display adult stem cell properties of self-renewal and differentiation in both epithelium and stroma of the human endometrium, probably responsible for in its immense regenerative capacity. Epithelial stem cells might be located in the basal layer of endometrium. Prospectively isolated CD133(+) cells and/or side population (SP) cells in endometrial cancer were capable of initiating tumor formation and of recapitulating the phenotype of the original tumor, and therefore are candidate for endometrial cancer stem cells. These studies help us to understand the mechanisms of endometrial regeneration as well as endometrial carcinogenesis and will hopefully help in establishing novel molecular-based cancer therapies targeting stem cells.