Figure 7.

A proposed model for FGF-8 action in prostate. (A) Increased levels of FGF-8b are secreted by the epithelial cells. It affects both the epitheliumand the stroma (autocrine and paracrine effects, pink arrows). (B) The affected stroma presents features of reactive stroma, such as increased amount of fibroblasts, inflammation, and angiogenesis. Altered stroma secretes connective tissue growth factor (CTGF), SPP1, and other (unidentified) factors that can affect the epithelium. The disturbed cross talk (indicated by green arrows) between stromal and epithelial compartment together with increased amounts of FGF-8b induce proliferation and dedifferentiation of the epithelium, leading to the development of preneoplastic mPIN lesions. (C) Prolonged FGF-8b exposure and disturbed epithelial-to-stromal cross talk induces the epithelium and the stroma to develop atypical and malignant changes. AR-positive nuclei are presented by dark gray; AR-negative nuclei, light gray color.