Characterization of a Stem-like Subpopulation in Basal-like Ductal Carcinoma in Situ (DCIS) Lesions [Cell Biology]

December 2nd, 2013 by Li, Q., Eades, G., Yao, Y., Zhang, Y., Zhou, Q.

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 which possess ALDH1 activity. We found that these cells show enhanced migration potential compared to non-stem DCIS cells. We also found that the chemopreventive agent sulforaphane (SFN) 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.