Fig. 3: Type I IFN activation in astrocytes promotes brain metastasis.
a Increased IFN response genes in astrocytes cocultured with BrM cells in vitro. Human astrocytes are cocultured with breast cancer MDA231-BrM cells. Mouse astrocytes are cocultured with breast cancer E0771-BrM and melanoma Yumm1.7-BrM. The expression levels of IFN response genes are measured by RT-PCR. Al cultured alone, Co cocultured. Representative data of 3 biologically independent experiments for each BrM cell. b–e Type I IFN signaling in astrocytes. b Human astrocytes are treated with conditioned media (CM) and type I IFN response genes are detected by RT-PCR. CM from astrocyte-BrM coculture (Co) or cultured alone (AL) are pretreated with either neutralizing antibody against IFNAR1 or the matched IgG control antibody (Ctrl). Representative data of 3 biologically independent experiments. c Astrocyte specific IFNAR1 knockout mice. d RT-PCR results of the type I IFN response gene, Ifit1, in the astrocytes cocultured with BrM cells in vitro. Primary cultured astrocytes are isolated from transgenic mice. Cre−, Gfap-Cre−/−; Ifnar1f/f mice; Cre+, Gfap-Cre+/−; Ifnar1f/f mice. Representative data of 3 biologically independent experiments for each BrM cell. e RT-PCR results of type I IFN response genes, Ifit1 and Isg15, in the astrocytes from brain metastatic lesions in vivo. From the experimental mice developed with brain metastasis, the metastatic lesions (BrM+) and matched metastasis-free tissues (BrM−) are isolated based on the luciferase signals in BLI. Data are merged samples from 2 biologically independent experiments. E0771 model (4 pairs for both Cre+ and Cre−). Yumm1.7 model (Cre−: 3 pairs; Cre+: 4 pairs). Source data are provided as a Source data file. f Type I IFN signaling in astrocytes facilitates brain metastasis. Breast cancer E0771-BrM, A7C11-BrM and melanoma Yumm1.7-BrM are injected into Cre- or Cre+ mice. Quantification of brain lesions by BLI. Data are merged from 3 biologically independent experiments and presented as mean ± S.E.M. P values are from unpaired two-tailed t test. Female mice: E0771 model (Cre−: n = 13; Cre+: n = 16); A7C11 model (Cre−: n = 8; Cre+: n = 11). Male mice: E0771 model (Cre−: n = 9; Cre+: n = 16); Yumm1.7 model (Cre−: n = 11; Cre+: n = 4). Source data are provided as a Source data file.
