title: Characterization of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Nadire
authors.initials: N
authors.lastname: Duru
authors.affiliation: Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Ramkishore
authors.initials: R
authors.lastname: Gernapudi
authors.affiliation: Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Pang-Kuo
authors.initials: PK
authors.lastname: Lo
authors.affiliation: Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolfson
authors.affiliation: Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Yongshu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology / Q000473:pathology*; D051927:CD24 Antigen / Q000032:analysis*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D039503:Integrin alpha6 / Q000032:analysis*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000502:physiology; D055748:SOXB1 Transcription Factors / Q000502:physiology
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D039503:Integrin alpha6; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: DCIS; cancer stem cells; non-coding RNAs; single cell cloning; tumor heterogeneity