Irradiation effect on osteoclastogenesis stimulated by breast cancer cells.

To examine the effects of carbon ion and gamma ray irradiation on cancer-induced osteoclastogenesis, mouse calvaria MC3T3-E1 cells were cultured with conditioned medium from irradiated and non-irradiated MCF7 human breast cancer cells. The authors examined RANKL and OPG mRNA expression in osteoblastic MC3T3-E1 cells following treatment with conditioned MCF7 medium. Co-cultured MC3T3-E1 and bone marrow cells treated with conditioned medium from irradiated MCF7 cells showed decreased numbers of osteoclasts, assessed using TRAP staining. Conditioned medium from control MCF7 cells elevated the RANKL/OPG mRNA ratio in MC3T3-E1 cells; this effect was suppressed by carbon ion irradiation of the MCF7 cells. These data demonstrate that indirect interactions between breast cancer cells and MC3T3-E1 cells induce osteoclastogenesis in vitro through modulation of RANKL expression and that this process is suppressed by carbon ion irradiation.