Alterations in expression of basic fibroblast growth factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer

Fibroblast growth factors (FGFs) play an important role in the growth and m aintenance of the normal prostate. There is increasing evidence from both a nimal models and analysis of human prostate cancer cell lines that alterati ons of FGFs and/or FGF receptors (PGFRs) may play an important role in pros tate cancer progression. To better define the role of FGF2 and FGF7 in huma n prostate cancer in vivo, we have quantified these two growth factors in c linically localized human prostate cancers and uninvolved prostate by ELISA and Western blotting and determined their localization by immunohistochemi stry. The expression of two of the primary receptors for these growth facto rs, FGFR-1 and FGFR-2, were also analyzed by immunohistochemistry and Weste rn blotting in these same samples. We have found that FGF2 is significantly increased in prostate cancers when compared with uninvolved prostate and t hat the FGF2 is present in the stromal fibroblasts and endothelial cells bu t not the cancer cells. In addition, we have observed overexpression of bat h FGFR-1 and FGFR-2 in the prostate cancer epithelial cells in a subset of prostate cancers and that such overexpression is correlated,vith poor diffe rentiation. Thus, there is both an increase in FGF2 concentration in prosta te cancers and an increased expression of a receptor capable of responding to this growth factor, establishing a potential paracrine stimulation of pr ostate cancer cells by the surrounding stromal cells, which may play an imp ortant role in prostate cancer progression.