High ALDH activity defines ovarian cancer stem-like cells with enhanced invasiveness and EMT progress which are responsible for tumor invasion

Abstract

Epithelial ovarian cancer (EOC) is highly metastatic and current therapeutics are unsatisfactory. Cancer stem/stem-like cells (CSCs/CSCLs) represent a rare population of undifferentiated oncogenic cells responsible for tumor initiation and maintenance. We identified ovarian cancer ALDHhigh (aldehyde dehydrogenase) population could perform not only strengthened CSCLs properties embodied in colony-formation, CSCs-markers expression, and tumorigenesis in vivo, but also a greater invasive capacity with advanced EMT progress and anti-apoptosis compared with ALDHlow cells. Furthermore, both the stemness and aggressive features, along with ALDHhigh percentages were in positive association with the invasiveness of cell lines for sorting, indicating the promotive role of ALDHhigh CSCLs in EOC neoplasia and metastasis, since the whole tumor was derived from the CSCLs with hyperactive self-renewal and aggression. Collectively, this study illustrates the interplay between ALDHhigh CSCLs and EOC invasion, and offers a novel application target for the EOC oncotherapy.