Characterization of a Stem-like Subpopulation in Basal-like Ductal Carcinoma in Situ (DCIS) Lesions |
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Authors: | Qinglin Li Gabriel Eades Yuan Yao Yongshu Zhang Qun Zhou |
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Affiliation: | From the Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201 |
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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. |
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Keywords: | Exosomes MicroRNA Breast Cancer Cancer Stem Cells Chemoprevention Basal-like DCIS Stem Cell Sulforaphane |
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