(A) Mammosphere assays were performed with SUM-159 cells in the presence of B27 supplement containing insulin (B27+) or without insulin (B27−). Scale bar, 200 μm.
(B and C) Mammosphere assays (B) and in vitro limiting-dilution assays (C) were performed with SUM-159 cells in B27+, B27−, or B27− medium supplemented with individual ligands (50 ng/mL).
(D–F) SUM-159 cells treated with non-targeting guide RNA (sgNT), IR knockout (KO) cells (IR−/−), or IGF1R KO cells (IGF1R−/−) were assayed for mammospheres in B27+ supplement (D), ALDH activity (E), and tumor initiation by in vivo limiting-dilution assay (F). For (E), the ALDH inhibitor DEAB was included as a negative control. For (F), cells were injected into the mammary fat pads of NCG mice in 10-fold serial dilutions at the concentrations indicated.
For (C) and (F), data are presented as a log-log plot, and the frequency of stem cells is calculated by extreme limiting-dilution analysis. The mammosphere data shown represent the mean ± SD of a representative experiment performed three times independently. The ALDH data shown represent the mean ± SD of six independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001.
See also Figure S1.