Abstract LB-261: Cancer stem cell characteristics exhibited by doxorubicin-selected drug-resistant breast cancer cells

Abstract

Abstract Background: Cancer stem cells (CSCs) are presumed to possess the virtually unlimited ability to proliferate while preserving self-renewal. These cells are also highly resistant to chemotherapeutics, a feature which correlates with overexpression of ATP-binding cassette (ABC) transporters. No reports to our knowledge have shown that prolonged continuous selection of cells for drug resistance enriches cancer stem-like cells. Methods: We examined parental and drug-selected breast cancer cell lines to determine whether there is a relationship between drug resistance and the presence of cells with a CSC phenotype. MCF-7/ADR cells, generated from weakly tumorigenic parental MCF7 cells by continuous exposure to increasing concentrations of doxorubicin, were examined by microarray analysis, flow cytometry, invasion, in vivo tumorigenicity and other CSC characteristics. The putative CSC population was also examined for expression of multidrug resistance (MDR) genes using TaqMan Low Density Arrays. Results: Pathway analysis showed that MCF-7/ADR cells express ABCB1 as well as genes with patterns similar to breast CSCs. MCF-7/ADR cells grow in 3D cultures as mammospheres, are highly invasive and tumorigenic. In contrast to parental cells, over 30% of MCF-7/ADR cells are CD44+/CD24-. The CD44+/CD24- cells have the ability to self-renew and overexpress many MDR genes when compared to the CD44+/CD24+ population. No enrichment in CD44+/CD24- or CD133+ populations was detected in MCF-7/MDR or other cells with forced expression of the ABCB1 transporter or MDR genes. Conclusions: Cells with characteristics of CSCs increased in number following selection for doxorubicin resistance. Based on our findings, we speculate that prolonged drug treatment in vivo may result in expansion of a CSC-like population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-261.