Isolation and Characterization of Cancer Stem Cells from High-Grade Serous Ovarian Carcinomas

Abstract

Background/Aims: In this study, a subpopulation of stem-like cells in human high grade serous ovarian carcinomas (ovarian cancer stem cells; OCSCs) were isolated and characterized. Methods: Primary high-grade serous ovarian carcinoma (HGSC) fresh biopsies were cultured under serum-free conditions to produce floating spheres. Sphere formation assay, including self-renewal, differentiation potential, chemo-resistance, and tumorigenicity were determined in vitro or in vivo. Results: OCSCs overexpressed stem cell genes (Oct-4, Nanog, Sox-2, Bmi-1, Nestin, CD133, CD44, CD24, ALDH1, CD117, and ABCG2). Immunostaining of spheres showed overexpressed Oct-4, Nanog, and Sox-2. These isolated tumor cells expanded as spheroid colonies for more than 30 passages. In contrast, adherent cells expressed high levels of CA125 and CK7. Flow cytometry analysis showed increased CSC markers (CD44, CD24, CD117, CD133, ABCG2, and ALDH1) in the spheroid cell population. OCSCs displayed higher chemoresistance to cisplatin or paclitaxel compared to adherent cells. Moreover, subcutaneous injection of 1 × 104 sphere-forming cells into NOD/SCID mice gave rise to new tumors similar to the original human tumors and could be passaged in mice. Conclusion: These results revealed that HGSCs are created and propagated by a small number of undifferentiated tumorigenic cells, and therapeutic targeting of these cells could be beneficial for treatment of HGSCs.

A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

“…Increasing evidence indicates that EOC itself is composed of a diverse group of tumors that can be further classified on the basis of distinctive morphologic and genetic features [1,2,[4][5][6]. Increasing evidence indicates that noncoding RNAs and cancer stem cells may contribute to the progression and metastasis of ovarian cancers [7][8][9][10]. Given the heterogeneity of human ovarian cancers, significant improvements in long-term survival will hinge on translating recent insights into the molecular and cellular characteristics of ovarian cancers into personalized treatment strategies, optimizing methods of screening or early detection, and developing novel therapeutics.…”

ABCG2-Meditated Multidrug Resistance and Tumor-Initiating Capacity of Side Population Cells from Colon Cancer

“…The plates were placed in a hatch box for 48 h. Then, each well was supplemented with CCK-8 (10 μl) solution and the plates were incubated for 3 h. The mean OD 450 values obtained are presented as a graph. The cell resistance in both groups was calculated using the following formula: cell resistance rate (%) = (experimental group OD 450 value/control group OD 450 value) × 100, as described previously [5]. …”

Review: Mechanotransduction in ovarian cancer: Shearing into the unknown

“…34,35 CSCs are defined as a small subset of cancer cells, with the capability of self-renewal, multilineage differentiation, tumor initiation, metastasis, and chemoresistance to conventional or targeted chemotherapies and radiotherapies. Ovarian CSCs are typically identified through expression of specific markers such as CD133, ALDH1A, CD24, CD117, CD44, [36][37][38][39] and micro ribonucleic acid (miRNA), as well as functional phenotypes such as self-renewal, production of heterogeneous progenies, and enhanced tumor formation capabilities.…”