Isolation and characterization of proliferative, migratory and multidrug-resistant endometrial carcinoma-initiating cells from human type II endometrial carcinoma cell lines

Abstract

Although the highly proliferative, migratory and multidrug resistant phenotype of human typeII endometrial carcinoma (EC) is well characterized, improved clinical treatments have not yet been developed. In this study, CD44 and CD133 were used as markers to screen, isolate and enrich carcinoma-initiating cells (CICs) from the human typeII EC cell lines KLE and ANCA3. Using flow cytometry, we identified a subpopulation of KLE and ANCA3 cells which express high levels of both CD44 and CD133 on the cell membrane. CD44+/CD133+ EC-CICs exhibited high levels of stemness marker genes, and possessed a higher migratory and invasive ability than CD44-/CD133- endometrial carcinoma cells (EC-CCs). CD44+/CD133+ EC-CICs were also more resistant to growth inhibition induced by the chemotherapeutic drugs cisplatin and paclitaxel. Additionally, CD44+/CD133+ EC-CICs readily established tumors invivo in a relatively short time. In conclusion, CD44+/CD133+ cells possessing the characteristics of CICs can be reliably sorted from KLE and ANCA3 human typeII EC cell lines, and represent a valuable model for studying cancer cell physiology and multidrug resistance. Further characterization of CD44+/CD133+ KLE and ANCA3 cells may have a profound impact on the selection of individual treatment strategies, clinical outcomes and design of the next generation of chemotherapeutic agents for typeII EC.