Stem cell characteristics of dormant cells and cisplatin-induced effects on the stemness of epithelial ovarian cancer cells

Abstract

Tumor dormancy is a common biological property of malignancies and a leading factor in treatment failure, metastasis and tumor recurrence. The present study generated mouse xenograft models by injection of PKH26-labeled SKOV3 ovarian cancer cells, which were divided into two groups: The control group (SKOV3-P tumors,) and the treatment group that generated resistant tumors following prolonged administration of cisplatin (SKOV3-R tumors). Administration of cisplatin resulted in inhibition of the tumor growth and SKOV3-R tumors coexisted with their host at a stable size. According to fluorochrome PKH26 retention, there were multiple cell clones (PKH26hi, PKH26low and PKH26neg cells) in the single cell line generated from xenograft tumors. PKH26hi subsets in SKOV3-P and SKOV3-R tumors were dormant cells, as the majority were arrested in G0/G1 phase and expressed high levels of the stem cell markers Oct-4, Nestin, CD117 and CD44. PKH26hi subsets also demonstrated greater clonogenic capability in vitro and tumorigenicity in vivo, as compared with PKH26low and PKH26neg cells. Notably, chemotherapy was demonstrated to lead to the enrichment and enhanced stem-like characteristics of dormant/slow-cycling PKH26hi cells. The results of the present study have demonstrated for the first time, to the best of our knowledge, that dormant tumor cells exhibit stem-like characteristics, and that cisplatin enhances these characteristics in epithelial ovarian cancer cells.