Expression of CD133 in endometrial cancer cells and its implications

Abstract

Cancer stem cells are an attractive therapeutic target for cancer. The present study examined stem cell characteristics of CD133+ cells isolated from endometrial cancer. Phenotypic characteristics, proliferation, migration, anchorage-independent growth, chemoresistance, gene expression profile and tumorigenicity of CD133+ tumor cells were assessed. Primary tumor exhibited immunoreactivity for CD133. Endometrial CD133+ tumor cells enhanced proliferation rate, colony formation, chemotaxis migration ability, and chemoresistance to cisplatin, paclitaxel, and doxorubicin than CD133-cells. CD133+ cells expressed more cancer stem cells markers such as EpCAM, aldehyde dehydrogenase 1 and insulin-like growth factor-1 receptor than CD133-cells. Moreover, CD133+ cells also increased expression of embryonic stem cell markers including oct4, nanog, sox2, and cmyc than CD133-cells. Finally, CD133+ tumor cells could generate xenograft but not CD133-tumor cells. CD133 and Ki67 were extensively expressed in the xenograft. In conclusion, endometrial CD133+ tumor cells displayed cancer stem cell characteristics and might represent a valuable tool for identifying endometrial cancer stem cells and hence a potential therapeutic target.

Targeting endometrial cancer stem cell activity with metformin is inhibited by patient-derived adipocyte-secreted factors

“…This is the first study, however, in which the two populations of cells with cancer stem cell activity have been directly compared at a functional and genetic level. Ding et al investigated stem cell gene expression in CD133 +ve cells, noting that they had significantly increased expression of SOX2 and NANOG as well as EPCAM (22). This contrasts with the findings described here, where RNA expression of all stem cell and epithelial markers was significantly lower in CD133 +ve compared with CD133 -ve cells.…”

“…In order to study the unique characteristics of these cells in more detail, two broad means of identifying and separating these cells from the bulk tumour population are frequently employed; detection of cell surface markers and enzyme activity, and the use of functional assays. Expression of CD133, a glycosylated pentaspan membrane protein, has been shown to be restricted to undifferentiated cells, and a population of CD133 +ve cells has been described in primary endometrial tumours that demonstrate many of the characteristics of cancer stem cells, including self-renewal, multipotency and increased tumour formation in immunodeficient mice (20)(21)(22)(23). Similar traits are exhibited by endometrial cancer cells with high activity levels of the aldehyde dehydrogenase (ALDH) enzyme, which plays a critical role in retinoic acid signalling, including increased colony and tumour forming capacity, invasive potential and resistance to the cytotoxic effects of cisplatin chemotherapy (24)(25)(26).…”

Differential gene expression induced by Verteporfin in endometrial cancer cells

“…Recently Ding et al . studied the characteristics of CD133 + cells isolated from endometrial cancer 56 . They proposed that CD133 + cells increased expression of embryonic stem cells markers including Oct4, Nanog, Sox2 than CD133 − cells.…”

Targeting Endometrial Cancer Stem Cell Activity with Metformin Is Inhibited by Patient-Derived Adipocyte-Secreted Factors

“…In order to study the unique characteristics of these cells in more detail, two broad means of identifying and separating these cells from the bulk tumour population are frequently employed; detection of cell surface markers and enzyme activity, and the use of functional assays. Expression of CD133, a glycosylated pentaspan membrane protein, has been shown to be restricted to undifferentiated cells, and a population of CD133 +ve cells has been described in primary endometrial tumours that demonstrate many of the characteristics of cancer stem cells, including self-renewal, multipotency and increased tumour formation in immunodeficient mice [20,21,22,23]. Similar traits are exhibited by endometrial cancer cells with high activity levels of the aldehyde dehydrogenase (ALDH) enzyme, which plays a critical role in retinoic acid signalling, including increased colony and tumour forming capacity, invasive potential and resistance to the cytotoxic effects of cisplatin chemotherapy [24,25,26].…”