Differential expression of specific FGF ligand and receptor isoforms during angiogenesis associated with prostate...

The aim of this study was to elucidate how changes in temporal and spatial expression patterns of individual components of the fibroblast growth factor (FGF) signaling axis correlate with prostate cancer-associated angiogenesis to contribute to the progression of this disease.

The temporal and spatial expression patterns of specific FGF ligands and receptors were characterized by immunoblot, in situ hybridization, and immunohistochemical analyses in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

We detected expression of high molecular weight isoform of FGF-2 in PIN lesions and detected both high and low molecular weight isoforms of FGF-2 in advanced tumors. Expression of the mRNA encoding the FGFR1iiib isoform was found to be specifically and differentially expressed in tumor vasculature in TRAMP but was not detected in prostate-associated vasculature in nontransgenic mice. Expression of the FGFR2iiic isoform was observed to be elevated in the epithelial component of PIN lesions in TRAMP mice.

By using the TRAMP model, the expression of FGFR1iiib in intraductal vasculature and expression of FGF-2 protein were found to be concomitant with the emergence of PIN. These observations implicate specific changes in the FGF axis with the initiation and progression of prostate cancer and underscore the utility of animal models to identify specific molecular changes in early disease.