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: Nadire Duru, Ramkishore Gernapudi, Pang-Kuo Lo, Yuan Yao, Benjamin Wolfson, Yongshu Zhang, Qun Zhou
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 30 Pg. 47511-47525 (Jul 26 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27374087 (Publication Type: Journal Article)

Chemical References

• CD24 Antigen
• CD24 protein, human
• CD44 protein, human
• Hyaluronan Receptors
• Integrin alpha6
• Octamer Transcription Factor-3
• POU5F1 protein, human
• SOX2 protein, human
• SOXB1 Transcription Factors

Topics

• Animals
• Breast Neoplasms (etiology, pathology)
• CD24 Antigen (analysis)
• Carcinoma, Intraductal, Noninfiltrating (pathology)
• Cell Line, Tumor
• Cell Movement
• DNA Methylation
• Female
• Humans
• Hyaluronan Receptors (analysis)
• Integrin alpha6 (analysis)
• Mice
• Neoplastic Stem Cells (pathology)
• Octamer Transcription Factor-3 (physiology)
• SOXB1 Transcription Factors (physiology)