Cytokines, interleukin (IL)-1alpha, IL-1beta, IL-3, IL-6, macrophage colony stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF-alpha) as well as parathyroid hormone-related protein (PTHrP) have been shown to enhance the osteoclast activity. To investigate mechanisms of the development of bone metastasis of prostatic cancers, expression of these cytokines and PTHrP was examined immunohistochemically in prostatic cancers of patients administered no prior therapy or endocrine therapy. All cytokines and PTHrP were stained in the cytoplasm of the epithelium of non-cancerous prostatic glands, and IL-3 and IL-6 were stained in the cytoplasm of smooth muscle cells besides epithelial cells of non-cancerous prostatic glands. Incidences of positivity of staining in prostate cancers of patients administered no prior therapy were 100% for IL-1alpha, IL-1beta, IL-6, M-CSF and TNF-alpha, 20% for IL-3, and 80% for PTHrP. Incidence of prostatic cancers stained positively for IL-1alpha and IL-1beta decreased significantly in patients administered endocrine therapy, but those for IL-3, IL-6, M-CSF, TNF-alpha and PTHrP did not change significantly. The present results suggest that prostatic cancers produce various cytokines, IL-1alpha, IL-1beta, IL-3, IL-6, M-CSF and TNF-alpha, as well as PTHrP, and that expression of these cytokines and PTHrP except IL-1alpha and IL-1beta is not under androgen control. Cytokines and PTHrP produced by prostatic cancers may play a role in the development of bone metastasis of prostatic cancers.

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