Abstract 4369: Eradication of chemotherapy-resistant CD44+ human ovarian cancer stem cells in C.B-17/SCID mice by intraperitoneal administration of Clostridium Perfringens Enterotoxin (CPE)

Abstract

Abstract Emerging evidence has suggested that the capability to sustain tumor formation, growth and resistance to chemotherapy in ovarian as well as other human malignancies, exclusively resides in a small proportion of tumor cells termed cancer stem cells (CSC). If this hypothesis is correct, different therapeutic approaches need to be considered for the elimination of the cancer stem cell population. During the characterization of CD44+ ovarian CSC we found a high expression of the genes encoding for claudin-4. Because this tight junction protein is the natural high affinity receptor for the cytotoxic effect of Clostridium Perfringens Enterotoxin (CPE), we have extensively investigated the sensitivity of ovarian CSC to CPE treatment in vitro and in vivo. We report that CD44+ ovarian CSC expressed claudin-4 gene at significantly higher levels when compared to matched autologous CD44- ovarian cancer cells and, regardless of their higher resistance to chemotherapeutic agents, died within 1 hr to the exposure to 1.0 μg/mL of CPE in vitro. Importantly, multiple intraperitoneal (i.p.) administration of sublethal doses of CPE in SCID mouse harboring established xenografts of chemotherapy resistant CD44+ ovarian CSC had a significant inhibitory effect on tumor progression leading to the cure and/or long term survival of all treated animals (p = 0.001). CPE may represent an unconventional, potentially highly effective strategy to eradicate chemotherapy resistant CSC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4369. doi:10.1158/1538-7445.AM2011-4369