Fig. 7: Pharmacological inhibition of PDGFRα with imatinib limits metastatic outgrowth of ER+ DTCs.
a, CellTiter-Glo analysis of ER+ tumor cells and fibroblasts after 72 h of vehicle or imatinib (1 µM) treatment (representative data of two independent repeats, multiple cell lines). b, TSAE1 cells were injected intravenously into young BALB/c mice, with mice receiving vehicle or imatinib as indicated (n = 5 mice per group). Middle, lung metastatic burden (day 15), with representative lung sections (scale bar, 5 mm). Bottom, lungs were stained for α-SMA, and metastatic deposits were scored for the number of α-SMA-positive cells (Extended Data Fig. 10g), with representative images (scale bar, 500 µm). c, ZR-75-1-mChLuc2 cells were injected intravenously into young NSG mice, with mice receiving vehicle or imatinib treatment as indicated (n = 6 mice per group). Middle left, whole-body IVIS signal on day 14. IVIS signal quantification, with representative images (scale bar shows radiance, p s−1 cm−2 sr−1). Middle right, quantification of ex vivo IVIS signal in livers (day 21). Bottom left, number of liver metastatic deposits. Bottom right, percentage of tumor deposits in the lungs that are single cells, doublets, 3–5 tumor cells, 6–10 tumor cells or >10 tumor cells. d, TSAE1 tumor cells transduced with shNTC1 or shPdgfc1 were inoculated intravenously into young BALB/c mice, which were treated with vehicle or imatinib as indicated (n = 5 mice per group). Metastatic lung burden (day 14), with representative lung sections shown (scale bar, 5 mm). Data are presented as mean values; ±s.e.m. (b–d); two-tailed t-test (b,c (top left)), two-tailed Mann–Whitney U-test (c, top right and bottom) or two-way ANOVA with multiple comparisons (d).
