Fig. 4: Tumor cell-derived PDGF-C in ER+ metastatic outgrowth.
a, Pdgfc expression (RT–qPCR) in TSAE1 cells transduced with shNTC1, shNTC2, shPdgfc1 or shPdgfc5. Representative of five independent repeats. b, In vitro proliferation of TSAE1 cells transduced with shNTC or shPdgfc. Representative of two independent repeats. c, TSAE1 cells transduced with shNTC or shPdgfc were injected intravenously into young BALB/c mice (n = 5 mice per group). Metastatic lung burden (day 14), with representative H&E-stained sections (scale bar, 5 mm). d, HRM1 cells transduced with shNTC or shPdgfc (Extended Data Fig. 7a,b) were injected intravenously into young FVB mice (n = 5 mice per group). Metastatic lung burden (day 30). Two mice with shPdgfc tumors had no metastatic deposits. Representative H&E-stained sections (scale bar, 5 mm). e, TSAE1 cells transduced with shNTC or shPdgfc were injected intravenously into bleomycin-treated young BALB/c mice (n = 5 mice per group) as described in Fig. 2e. Metastatic lung burden (day 11 after TSAE1 inoculation), with representative H&E-stained sections (scale bar, 5 mm). f, TSAE1 cells transduced with shNTC or shPdgfc were injected orthotopically into young BALB/c mice (n = 6 mice per group). Left, tumor growth. Right, quantification of lung metastatic deposits (day 28; shNTC and shPdgfc, n = 12 mice per group). Bottom, representative H&E-stained sections (scale bar, 500 µm). See Extended Data Fig. 9a,b for primary tumor immunostaining. g, TSAE1 cells carrying control vector (EV) or expressing Pdgfc (Pdgfc o/e). Left, Pdgfc expression (RT–qPCR) in TSAE1 tumors (EV, n = 6 mice; Pdgfc overexpression, n = 5 mice). Right, in vitro proliferation. Representative of two independent repeats. h, Young BALB/c mice were injected orthotopically with TSAE1 cells carrying EV (n = 6 mice) or overexpressing (o/e) Pdgfc (n = 5 mice). Mice were culled on days 30–35. Left, tumor growth for individual mice. Right, quantification of lung metastatic deposits. Data are presented as mean values ± s.e.m. (c–h); one-way ANOVA with multiple comparisons (c–e) or two-tailed t-test (f–h).
