Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro

Cancer cells metastasized to bone induce osteoclastogenesis for bone destru ction. Coculture of either mouse melanoma B16 or breast cancer Balb/c-MC ce lls with mouse bone marrow cells (BMCs) induced osteoclast-like cells, whic h were not observed when cancer cells were segregated from BMCs, Osteoclast differentiation factor (ODF), also known as receptor activator of NF-KB li gand (RANKL), is a direct mediator of many osteotropic factors. Neither BMC s, B16 nor Balb/c-MC cells alone expressed ODF mRNA. However, coculture of these cancer cells with BMCs induced ODF expression, which was prevented by indomethacin, Moreover, the coculture with cancer cells inhibited secretio n of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF), an in hibitory decoy receptor for ODF, from BMCs, Thus, enhanced osteoclastogenes is in the presence of cancer cells might be due to an increase in ODF activ ity. These results suggest that interactions between cancer cells and BMCs induce ODF expression and suppress OPG/OCIF level in metastatic foci result ing in pathological osteoclastogenesis for bone destruction. (C) 2000 Acade mic Press.