biostudies-literatureMcGowan PMIntramural NIH HHSCIHR834-44https://www.ebi.ac.uk/biostudies/studies/S-EPMC3140630biostudies-literatureUnknown9(7)Brain metastasis from breast cancer is an increasingly important clinical problem. Here we assessed the role of CD44(hi)/CD24(lo) cells and pathways that regulate them, in an experimental model of brain metastasis. Notch signaling (mediated by γ-secretase) has been shown to contribute to maintenance of the cancer stem cell (CSC) phenotype. Cells sorted for a reduced stem-like phenotype had a reduced ability to form brain metastases compared with unsorted or CD44(hi)/CD24(lo) cells (P < 0.05; Kruskal-Wallis). To assess the effect of γ-secretase inhibition, cells were cultured with DAPT and the CD44/CD24 phenotypes quantified. 231-BR cells with a CD44(hi)/CD24(lo) phenotype was reduced by about 15% in cells treated with DAPT compared with DMSO-treated or untreated cells (P = 0.001, ANOVA). IMolecular cancer research : MCRNotch1 inhibition alters the CD44hi/CD24lo population and reduces the formation of brain metastases from breast cancer.PMC3140630ZIA BC010538Palmieri DSteeg PSChambers AFMcGowan PMFoster PJSimedrea CRibot EJAllan ALfalseNotch1 inhibition alters the CD44hi/CD24lo population and reduces the formation of brain metastases from breast cancer.Brain metastasis from breast cancer is an increasingly important clinical problem. Here we assessed the role of CD44(hi)/CD24(lo) cells and pathways that regulate them, in an experimental model of brain metastasis. Notch signaling (mediated by γ-secretase) has been shown to contribute to maintenance of the cancer stem cell (CSC) phenotype. Cells sorted for a reduced stem-like phenotype had a reduced ability to form brain metastases compared with unsorted or CD44(hi)/CD24(lo) cells (P < 0.05; Kruskal-Wallis). To assess the effect of γ-secretase inhibition, cells were cultured with DAPT and the CD44/CD24 phenotypes quantified. 231-BR cells with a CD44(hi)/CD24(lo) phenotype was reduced by about 15% in cells treated with DAPT compared with DMSO-treated or untreated cells (P = 0.001, ANOVA). I2011-01-01T00:00:00Z2011 Jul2026-03-15T21:05:25.578Z2025-08-13T03:06:24.193ZS-EPMC31406302166593710.1158/1541-7786.MCR-10-045710.1158/1541-7786.mcr-10-0457