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


Publication Type:

Source:

J Biol Chem, Volume 289, Issue 3, p.1303-12 (2014)

Keywords:

Animals, Anticarcinogenic Agents, Antigens, CD24, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Cell Line, Tumor, Cell Movement, Female, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Humans, Integrin alpha6, Isoenzymes, Isothiocyanates, Mice, Mice, Nude, MicroRNAs, Neoplasm Proteins, Neoplastic Stem Cells, Retinal Dehydrogenase, RNA, Neoplasm, Signal Transduction

Abstract:

<p>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.</p>