Characterization of the CD49f+/CD44+/CD24− single-cell derived stem cell population in basal-like DCIS cells
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Nadire Duru1, Ramkishore Gernapudi1, Pang-Kuo Lo1, Yuan Yao1, Benjamin Wolfson1, Yongshu Zhang1, Qun Zhou1
1Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Qun Zhou, email: [email protected]
Keywords: tumor heterogeneity, single cell cloning, cancer stem cells, DCIS, non-coding RNAs
Received: March 29, 2016 Accepted: June 09, 2016 Published: June 21, 2016
The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f+/CD44+/CD24− surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f+/CD44+/CD24− DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition.
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