A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
FGF-8 is involved in bone metastasis of prostate cancer
Tekijät: Valta MP, Tuomela J, Bjartell A, Valve E, Väänänen HK, Härkönen P
Julkaisuvuosi: 2008
Journal: International Journal of Cancer
Tietokannassa oleva lehden nimi: International journal of cancer
Lehden akronyymi: Int J Cancer
Vuosikerta: 123
Numero: 1
Aloitussivu: 22
Lopetussivu: 31
Sivujen määrä: 10
ISSN: 0020-7136
eISSN: 1097-0215
DOI: https://doi.org/10.1002/ijc.23422
Tiivistelmä
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.
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.
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