Fig. 1

Increased active YAP1 and FAPα levels in fibroblasts are associated with tissue fibrosis and cancer progression in NPC. A Representative IHC images of PDGFRα/β, YAP1 and FAPα, and trichrome staining in NPC tumor fibroblasts. Immunoreactivity was analyzed in FFPE consecutive NPC tissue sections. Scale bar, 50 μm. B–D Correlation analysis of nuclear YAP1 and FAPα expression (B), nuclear YAP1 and trichrome signals (C), and FAPα and trichrome signals (D) based on IHC scores in tumor sample fibroblasts (Spearman’s correlation test). E–F Statistical analysis of nuclear YAP1 (E) and FAPα (F) expression in stromal fibroblasts of NPC tumors obtained from patients with complete tumor remission or distant metastasis after treatment (chi-square test). G–H Kaplan–Meier metastasis-free survival curves of NPC patients based on nuclear YAP1 levels (G) or FAPα levels (H). I TEM analysis of HK1EBV cell-derived exosomes. Scale bar, 200 nm. J Western blot analysis of exosomal proteins. Cell and exosome lysates extracted from rAkata cells, which were used as EBV-positive controls. Cell lysates and exosomes derived from 2-day–cultured supernatants of HK1EBV cells or rAkata cells. K Representative IHC images of PDGFRα/β, active YAP1 and FAPα, and trichrome staining in NPC xenografts. Scale bar, 20 μm. L Tumor growth in NPC xenografts. HK1EBV cells, HK1EBV cells together with fibroblasts, or HK1EBV cells together with exosome-treated fibroblasts were subcutaneously injected into the legs of mice (n = 8–9 mice/group). Data are presented as means and SEMs (***p < 0.001, compared with the other two groups; paired t test). M–O Correlation analyses based on IHC scores in NPC xenografts (Spearman’s correlation test)