Extended Data Figure 8: Effects of anti-DR6 antibody and DR6-Fc on tumour metastasis.
From: Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis
a–i, Quantification of MDA-MB-231 TC-induced EC necroptosis (a, c, g), transmigrated TCs over an endothelial layer (b, e, h), B16 TC-induced EC necroptosis after i.v. injection into C57BL/6 WT animals (d) or lung metastases 12 d after i.v. injection of LLC1 TCs into WT animals (f, i) upon treatment with an anti-DR6 antibody (5D10) (a, b, f), etanercept (c–e) or the extracellular domain of DR6 fused to DR6 (DR6-Fc) (g–j). Animals were treated shortly before and 3 h after TC injection (d) as well as 6 h after TC injection (f, i). PBS, an IgG1 antibody or the Fc domain of IgG1 or IgG2A (IgG1-Fc, IgG2A-Fc) served as controls. g, Representative confocal images of lung sections taken 6 h and images of whole lungs taken 12 d after i.v. injection of B16 TCs into WT animals treated with IgG2A-Fc (control) or DR6-Fc shortly before and at 3 h after TC injection (plus at 6 h for the 12 d experiment); scale bar, 50 μm. Shown are representative data of three independent experiments with mean values ± s.e.m. (a–e, g, h) or ± s.d. (f, i) from biological sextuplicates (n = 6) (a–c, e, g, h) or from n = 3 (d) or n = 4 (f, i) animals per group. *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant. Two-way ANOVA and Bonferroni’s post hoc test (a–d, g, h) or unpaired, two-tailed Student’s t-test (e, f, i).
