FGF‐8 is involved in bone metastasis of prostate cancer

前列腺癌 骨转移 医学 转移 病理 前列腺 癌症 免疫组织化学 成骨细胞 PCA3系列 癌症研究 内科学 生物 生物化学 体外
作者
Maija Valta,Johanna Tuomela,Anders Bjartell,Eeva Valve,H. Kalervo Väänänen,Pirkko Härkönen
出处
期刊:International Journal of Cancer [Wiley]
卷期号:123 (1): 22-31 被引量:86
标识
DOI:10.1002/ijc.23422
摘要

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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