Department of Gynecologic Oncology, Women's Hospital, Zhejiang University, Hangzhou, China.
Cell Mol Life Sci. 2010 Nov;67(22):3915-25. doi: 10.1007/s00018-010-0420-9. Epub 2010 Jun 12.
Cancer stem cells (CSCs) play an important role in the development, invasion, and drug resistance of carcinoma, but the exact phenotype and characteristics of ovarian CSCs are still disputable. In this study, we identified cancer stem cell-like cells (CSC-LCs) and investigated their characteristics from the ovarian adenocarcinoma cell line 3AO. Our results showed that CSC-LCs were enriched in sphere-forming test and highly expressed CD44(+)CD24⁻. The spheres and CD24⁻ cells possessed strong tumorigenic ability by transplantation into nonobese diabetic/severe combined immunodeficient mice. CD44(+)CD24⁻ cells expressed stem cell markers and differentiated to CD44(+)CD24(+) cells by immunofluorescence assay and fluorescence-activated cell-sorting analysis. In vitro experiments verified that CD44(+)CD24⁻ cells were markedly resistant to carboplatin and paclitaxol. In conclusion, our study identifies the CD44(+)CD24⁻ phenotype, self-renewal, high tumorigenicity, differentiation potential, and drug resistance of ovarian CSC-LCs. Our findings may provide the evidence needed to explore a new strategy in the treatment of ovarian cancer.
癌症干细胞 (CSCs) 在癌的发展、侵袭和耐药性方面发挥着重要作用,但卵巢 CSCs 的确切表型和特征仍存在争议。在本研究中,我们从卵巢腺癌细胞系 3AO 中鉴定出具有癌症干细胞样特性的细胞 (CSC-LCs),并研究了它们的特性。我们的结果表明,CSC-LCs 在球体形成试验中富集,并高度表达 CD44(+)CD24⁻。球体和 CD24⁻细胞通过移植到非肥胖型糖尿病/严重联合免疫缺陷小鼠中具有很强的致瘤能力。CD44(+)CD24⁻细胞表达干细胞标记物,并通过免疫荧光和流式细胞术分析分化为 CD44(+)CD24(+)细胞。体外实验证实 CD44(+)CD24⁻细胞对卡铂和紫杉醇有明显的耐药性。总之,本研究鉴定了卵巢 CSC-LCs 的 CD44(+)CD24⁻表型、自我更新、高致瘤性、分化潜能和耐药性。我们的发现可能为探索卵巢癌治疗的新策略提供所需的证据。