Fig. 6

The PI3K-Akt signaling pathway mediates macrophage exosomal ApoE-induced aggressiveness in GC cells. a Representative immunofluorescence and quantification of actin staining (green) using phalloidin (scale bar, 10 µm) in MFC cells treated with M2-Exos from Apoe−/− or WT BMDMs. Shown is the mean ± s.d. of three independent experiments. b Western blot analysis of EMT proteins after MFC cells were treated with M2-Exos from Apoe−/− or WT BMDMs. c Western blot analysis of PI3K-Akt signaling proteins after MFC cells were treated with exosomes derived from Apoe−/− or WT M2 macrophages. d Western blot analysis of pAkt/Akt proteins in MFC cells treated with 0.2 µM of PI3K inhibitor (wortmannin) with or without M2-Exos from WT or Apoe−/− M2 macrophage. e Proposed working model. Exosomes secreted by M2-type TAMs transfer ApoE into adjacent GC cells, leading to PI3K-Akt-mTOR signaling pathway activation in tumor cells. PI3K-Akt pathway activation in tumor cells increases cytoskeletal remodeling, facilitating the migratory potential of the tumor cell. Error bars represent mean ± s.d. *P < 0.05, **P < 0.01; n.s. not significant; by one-way ANOVA with Dunnett’s multiple-comparison test (a)