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J Biol Chem. 2014 Jan 17;289(3):1303-12. doi: 10.1074/jbc.M113.502278. Epub 2013 Dec 2.

Characterization of a stem-like subpopulation in basal-like ductal carcinoma in situ (DCIS) lesions.

Author information

1
From the Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201.

Abstract

Previously, we found that basal-like ductal carcinoma in situ (DCIS) contains cancer stem-like cells. Here, we characterize stem-like subpopulations in a model of basal-like DCIS and identify subpopulations of CD49f+/CD24- stem-like cells that possess aldehyde dehydrogenase 1 activity. We found that these cells show enhanced migration potential compared with non-stem DCIS cells. We also found that the chemopreventive agent sulforaphane can target these DCIS stem-like cells, reduce aldehyde dehydrogenase 1 (ALDH1) expression, and decrease mammosphere and progenitor colony formation. Furthermore, we characterized exosomal trafficking of microRNAs in DCIS and found that several microRNAs (miRs) including miR-140, miR-29a, and miR-21 are differentially expressed in exosomes from DCIS stem-like cells. We found that SFN treatment could reprogram DCIS stem-like cells as evidenced by significant changes in exosomal secretion more closely resembling that of non-stem cancer cells. Finally, we demonstrated that exosomal secretion of miR-140 might impact signaling in nearby breast cancer cells.

KEYWORDS:

Basal-like DCIS Stem Cell; Breast Cancer; Cancer Stem Cells; Chemoprevention; Exosomes; MicroRNA; Sulforaphane

PMID:
24297178
PMCID:
PMC3894316
DOI:
10.1074/jbc.M113.502278
[Indexed for MEDLINE]
Free PMC Article

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