Extended Data Figure 10: Inhibition of gap junction activity prevents brain metastatic outgrowth.
From: Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer
a–d, After treatment with tonabersat or meclofenamate (a), brain metastasis (b), primary tumour growth in mammary fat pads (c), or lung metastasis (d) was quantified by BLI. Data are mean ± s.e.m. (n = 2 independent experiments with 10 mice total in each group). e, Human astrocytes were treated with 200 μM tonabersat or 100 μM meclofenamate for 12 h before transfection with cGAMP (4 μg ml−1) using Lipofectamine 2000 or Lipofectamine alone. Conditioned media was collected 18 h later and assayed for human TNF and IFNα by ELISA (n = 2 biological replicates). f, g, Knockdown of Cx43 and PCDH7 in MDA231-BrM2 cells with tet-on inducible shRNA as assessed by RT–PCR (f) and western blotting (g), after doxycycline treatment in vitro (n = 2 independent experiments). h, Brain ex vivo BLI 14 days after inoculation of MDA231-BrM2 cells (n = 10 mice).
