Abstract A38: DDB2 suppresses tumorigenicity of ovarian cancer cells through reducing the subpopulation of cancer stem cells

Abstract

Abstract Ovarian cancer is an extremely aggressive disease associated with a high percentage of recurrence and chemotherapy resistance. Damaged DNA binding protein 2 (DDB2) is a 48-kDa protein originally identified as a component of the damage-specific DNA-binding heterodimeric complex DDB. Besides the known ability of DDB2 protein to bind ultraviolet (UV)-damaged DNA and serving as the initial damage recognition factor during nucleotide excision repair (NER). DDB2 was also reported to be involved in the promotion of apoptosis to reduce cisplatin resistance of ovarian cancer cells, control of cell migration, invasiveness and breast tumor progression, as well as suppression of metastasis of colon cancer through a transcriptional regulatory mechanism. Here we show that DDB2 overexpression in human ovarian cancer cell line CP70 suppressed its capability to recapitulate tumors in athymic nude mice, as well as the growth of these cells cultured in semisolid media. Flow cytometry analyses indicate that DDB2 overexpression in CP70 cells reduced the abundance of CD117+ cells and ALDH+ cells, which are believed to be markers of cancer stem cells (CSCs) in ovarian cancer. In contrast, downregulation of DDB2 in ovarian cancer cell line A2780 increased the percentage of ALDH+ cells. In addition, we analyzed the expression level of DDB2 in the putative CSCs isolated from various ovarian cancer cell lines, and demonstrated that DDB2 expression is decreased in the CSCs in comparison with their parental bulk tumor cells. Overexpression of DDB2 in the ovarian CSCs reduced the expression of CSC markers, e.g., Sox2 and Nanog. In addition, overexpression of DDB2 in CSCs isolated from ovarian cancer cell line SKOV-3 also decreased the tumorigenicity of these cells in NOD/SCID mice. In summary, our data suggest that DDB2 suppresses tumorigenicity of ovarian cancer cells through reducing the CSCs pool in cancer cells. Thus, increasing the expression of DDB2 may provide a molecular strategy to inhibit the recurrence of ovarian cancer. (Supported by NIH R01 grant CA151248 to QEW) Citation Format: Chunhua Han, Ran Zhao, John Kroger, Xingluo Liu, Qi-En Wang. DDB2 suppresses tumorigenicity of ovarian cancer cells through reducing the subpopulation of cancer stem cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A38.