title: Characterization of a stem-like subpopulation in basal-like ductal carcinoma in situ (DCIS) lesions.
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.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
authors.forename: Gabriel
authors.initials: G
authors.lastname: Eades
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.forename: Yongshu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051927:CD24 Antigen / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis; D017879:Isothiocyanates / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D012334:RNA, Neoplasm / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D051927:CD24 Antigen; C497889:CD24 protein, human; D039503:Integrin alpha6; D007527:Isoenzymes; D017879:Isothiocyanates; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D013454:Sulfoxides; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; C016766:sulforaphane
keywords: Basal-like DCIS Stem Cell; Breast Cancer; Cancer Stem Cells; Chemoprevention; Exosomes; MicroRNA; Sulforaphane