Abstract

To assess the potential effect of lanthanides(Ln)on the prevention of prostate cancer(PCa)bone metastasis,in this study we report the influence of Ln on PCa cells induced osteoblasts and osteoclasts differentiation.We cultured osteoblast-like MC3T3-e1 cells with conditioned medium(CM)from lanthanum(La)or gadolinium(Gd)treated DU145 cells.MC3T3-e1 differentiation increased in the presence of DU145 CM treated with La,whereas Gd treatment had no effect on MC3T3-e1 differentiation.Using RT-PCR arrays,we observed an increase in the expression of BMP6 genes in DU145 cells treated with La.Western blot analysis demonstrated that LaCl3 treatment increased phosphorylation of c-Jun NH(2)-terminal kinase(JNK).In addition,La reduced the expression of osteoclastogenesis-associated genes RANKL while increasing OPG expression in DU145 cells.Furthermore,La inhibited DU145 cells induced osteoclast formation in an in vitro coculture model of prostate cancer cells with osteoclast precursors generated from mouse bone marrow cells,while Gd failed to show the similar phenomenon in osteoclast differentiation.

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