Abstract 3024: Cancer stem-like cells in ovarian clear cell carcinoma are enriched in ALDH-high population associated with the accelerated scavenging system of reactive oxygen species

Abstract

Abstract In ovarian cancer cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian cancer stem-like cells (CSCs) are involved. Ovarian clear cell carcinoma is especially chemo-resistant among epithelial ovarian cancer subtypes. We first, examined the CSC markers (CD133,CD44, ALDH1) using the ovarian clear cell carcinoma tissues (n=81). Immunohistochemical staining revealed that high ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. Other makers are not related to clinical staging and prognosis. Clear cellcarcinoma cells (KOC-7C) are separated to ALDH-high and ALDH-low population by ALDEFLUOR assay and fluorescence-activated cell sorting. ALDH-high cells showed more quiescent character (G0/G1 phase) than ALDH-low cells. Recent studies have suggested that CSCs might have a high antioxidant capacity to keep cellular reactive oxygen species (ROS) at a low level that allows them to survive adverse conditions. We examined the cellular ROS level using Cell-ROX assay. ALDH-high cells contained the lower levels of ROS than ALDH-low cells. Also, ALDH-high cells showed an increased expression of in nuclear factor-E2-related factor 2 (Nrf2), a key transcriptional factor of the antioxidant system, associated with the increased antioxidant enzymes (SOD2, HO-1). Thus, ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemo-resistance in ovarian clear cell carcinoma. Citation Format: Tomoko Mizuno, Noriko Suzuki, Minako Mori, Hiroshi Makino, Tatsuro Furui, Naoki Ito, Akio Yamamoto, Kennichiro Morishige. Cancer stem-like cells in ovarian clear cell carcinoma are enriched in ALDH-high population associated with the accelerated scavenging system of reactive oxygen species. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3024. doi:10.1158/1538-7445.AM2014-3024