Science et thérapie du cancer

CD24+SSEA4+cells in Ovarian Carcinoma Cells Demonstrated the Characteristics as Cancer Stem Cells

Abstract

Fang Wang,Toshiko Yoshida, Motonori Okabe, Moustafa Fathy, Yi Sun, Chika Koike, Shigeru Saito and Toshio Nikaido

Object: Cancer stem cells (CSCs) have recently started attracting attention as targets cancer treatment. Despite many studies, markers of effective CSCs of heterogeneous ovarian carcinoma (OC) that can be directly used for medical treatment have not yet been reported. The aim of this research was to identify a new combination of surface markers for human ovarian CSCs.

Methods: Primary serous adenocarcinomas were obtained from patients with OC. FACS were used to decide cell surface marker to characterize and isolate cancer stem cells from primary human cancer tissues. RT-PCR methods were used for estimating the expression levels of mRNA, and immunohistochemistry confirmed the produce of the stemness relative protein after cell sorting. Xenograft model was used for the ability of tumorogenesis.

Results: We found that the cultured cells strongly expressed stemness genes such as c-myc, oct3/4, sox2, nanog, abcg-2, and bmi-1. They also expressed surface markers such as CD24, SSEA4, CD133, and CD47. The sub-population of CD24+ SSEA4+ double positive cells showed strong expression of Oct-4, and was able to form spheres much more than CD24-SSEA4+ cells, CD24+SSEA4-cells or CD24- SSEA4-double negative cells. Only 5 CD24+SSEA4+ cells formed spheres within 3 weeks. This sub-population formed the highest number of colonies in the soft agar colony assay. The CD24+SSEA4+ cells showed better growth in the presence of cisplatin than the other sub-populations. CD24+SSEA4+ cells were tumorigenic in all scid mice (4/4) within 2 months, with an injection of 100 cells/mouse.

Conclusion: These results suggested that CD24+SSEA4+double positive cells have characteristics similar to that of human ovarian tumor CSCs. It might be possible to develop effective new clinical therapies for human ovarian cancer (OC) using these cells as targets.