Abstract 4298: Identification of subpopulation with more defined characteristics of cancer stem cells in endometrial cancer

Abstract

Abstract [Background] Cancer stem cells (CSCs) have been known to be the major source of tumor propagation and might be an attractive therapeutic target. Our previous study showed that CD133+ Ishikawa and MFE 280 endometrial cancer cells have the ability of tumorigenicity, self-renewal and differentiation capacity in vitro and in vivo, while CD133- cells did not. Furthermore, CD133+ cells showed more resistance to cisplatin- or paclitaxel-induced cytotoxicity than CD133- cells. These results indicate that CD133 is the CSC maker in endometrial cancer cells. In the present study, we sought to identify the subpopulation with more defined CSC characteristics in endometrial cancer. [Methods] We examined the expression of CD133, CD44 and Hoechst 33342 side population (SP) marker by flow cytometry (FACS) in endometrial canecr cells. MIcroarray analysis was performed to investigate the molecules essential for the CSCs characteristics by 3D-Gene chip (TORAY). [Results] FACS analysis demonstrated that in the CD133+ Ishikawa and MFE280 cells, about 50% cells showed CD44 expression, whereas about 20% cells expressed it in CD133- cells. Isolated CD44+/CD133+ cells showed more extensive proliferation and tumorigenicity, compared with CD44+/CD133-, CD44-/CD133+ and CD44-/CD133- cells, indicating that the CD44+/CD133+ endometrial cancer cells have the potential of more defined CSCs. On the other hand, the ratio of SP fraction was similar in CD133+ and CD133- cells. Microarray analysis showed elevated expression of MT1-MMP and VEGF in CSCs, compared to non-CSCs. Invasion assay revealed that CSCs have more invasive property than non-CSCs. The inhibition of MT1-MMP gene by siRNA significantly reduced the invasive ability of CSCs. These results suggest that MT1-MMP is one of the critical molecules that generate biological features of CSC and may be a potential therapeutic target in endometrial cancer. [Conclusions] We demonstrated that CD44+/CD133+ cells might be more defined CSCs in endometrial cancer and identified important molecules essential for characterizing endometrial CSCs that might be a therapeutic target of this tumor type. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4298.