Fig. 7

SNAI2 is required for the procarcinogenic role of fibroblasts in an OC xenograft model. a Western blot showing the protein expression of SNAI2 and aSMA in a panel of primary CAFs isolated from metastatic tumor tissues of serous OC patients. b Left: Immunofluorescence staining of SNAI2 to verify the acquisition of SNAI2 expression in primary CAFs after Ade-SNAI2 transfection (left panel). Right: Western blot analysis confirmed the effect of the SNAI2 expressing adenovirus in increasing SNAI2 expression. c Representative bioluminescence images of mice (n = 8 each group) bearing SKOV3-Luc alone or co-injection with primary CAFs transfected with either Ade-NC or Ade-SNAI2 at 4 weeks after tumor implantation. Bar graph showing the quantification of the normalized total photon counts of the subcutaneous xenografts in each group. d Masson trichrome staining and quantification of the matrix content in tumor sections from mice in groups described in (c). e Representative aSMA staining images and quantification of the amount of myofibroblasts in xenograft tissues of the above groups. f Xenograft tissue stiffness was measured as Young’s Modulus and presented as the relative elastic modulus compared with that of the SKOV3 alone group. g Western blot analysis confirmed the silencing efficiency of sh-SNAI2 in reducing SNAI2 expression in the primary CAFs. h Representative bioluminescence images of mice (n = 8 each group) bearing SKOV3-Luc alone or co-injection with primary CAFs transfected with either sh-NC or sh-SNAI2 at 4 weeks after tumor implantation. Bar graph showing the quantification of the normalized total photon counts of the subcutaneous xenografts of each group. i Masson trichrome staining and quantification of the matrix content in tumor sections from mice in groups described in (h). j Representative aSMA staining images and quantification of the amount of myofibroblasts in xenograft tissues of the above groups. k Xenograft tissue stiffness was measured as Young’s Modulus and presented as the relative elastic modulus compared with that of the SKOV3 alone group. l Graphical illustration of the feed-forward regulation mechanism between matrix stiffness and SNAI2 to drive CAF activation, desmoplasia and tumor progression. Matrix stiffness promotes SNAI2 expression in stromal CAFs, which feeds back to maintain a stiff matrix and the subsequent SNAI2 mesenchymal signature that drives a reactive tumor stroma and facilitates tumor promotion. (*P < 0.05;**P < 0.01; ***P < 0.001)