Prostate cancer is the most common
malignancy of men in Western countries. Patients with advanced
prostate cancer suffer from incurable bone
metastases. Recent data indicate that interactions between
prostate cancer cells, osteoblasts, osteoclasts and the bone matrix are essential in the formation of bone
metastases. FGF-8 is widely overexpressed in
prostate cancer. Recently, FGF-8 has been found to affect both osteoblast and osteoclast differentiation. The aim of this study was to examine the role of FGF-8 in bone
metastasis of
prostate cancer. Immunohistochemistry was used to analyse FGF-8 expression in clinical samples of
prostate cancer bone
metastases. The functional significance of FGF-8 in growth of bone
metastasis and formation of bone lesions was verified by using intratibial inoculations of FGF-8 or mock transfected PC-3
prostate cancer cells in nude mice. Intratibial
tumors and bone lesions were analysed with X-ray, micro-CT and detailed histomorphometry using image analysis software and with immunostaining for
osteocalcin and
cathepsin K. Immunohistochemical analysis of tissue microarray of bone
metastases of human
prostate cancer showed that 76% of human bone
metastasis samples (n = 25 from 11 patients) were positive for FGF-8. FGF-8 increased the growth of intratibial
tumors and local formation of lytic and sclerotic lesions of bone. These results demonstrate that FGF-8 is expressed at a high frequency in bone
metastases of human
prostate cancer and that expression of FGF-8 in PC-3
prostate cancer cells increases their growth as intratibial
tumors and modulates formation of bone lesions in an in vivo model of
prostate cancer bone
metastasis.