Fig. 3: BCSC-secreted DKK1 enhances metastatic colonization.
From: Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis
a The schematic of co-implantation model. The 1 × 106 luciferase-labeled SUM159-luc cells were intravenously co-injected with 4 × 105 unlabeled mammosphere-enriched shCONT BCSCs, shDKK1 BCSCs or parental cells into the host mice. BLI was performed on the metastatic burden of SUM159-luc cells. b BLI was performed on the metastatic burden of SUM159-luc cells. c Immunohistochemical (IHC) staining of DKK1 in 15 pairs of human primary breast cancer and lymph node metastases. Scale bar: 50 μm. d Immunoblot assessment of DKK1 protein levels. e, f BLI (e) or H&E staining (f) of the lungs from mice orthotopically implanted with 2 × 106 MDA-MB-231-shCONT or -shDKK1 cells 4 weeks later. Scale bar: 100 μm. g BLI of the metastatic burden of mice intravenously injected with 1 × 106 MDA-MB-231-shCONT or -shDKK1 cells. h, i Immunofluorescent (IF) staining of Ki-67 and ALDH1 (h) or IHC staining of CDKN1B, CHEK1 and TGFB2 (i) in lung sections from mice intravenously injected with MDA-MB-231-shCONT or -shDKK1 cells. Scale bar in (h): 100 μm. Scale bar in (i): 50 μm. j BLI of the metastatic burden of mice intravenously injected with 1 × 106 SUM159-Vector or SUM159-DKK1 cells. k Kaplan–Meier plots of relapse-free survival (RFS) in the indicated population of breast cancer patients stratified according to tumor DKK1 expression. The data was analyzed in all molecular subtypes of breast cancer. Results are shown as mean ± S.D. *P < 0.05; **P < 0.01; ***P < 0.001; ns not significant (Paired two-tailed Student’s t test in (c) others unpaired two-tailed Student’s t test). Source data are provided as a Source Data file.
