Malignant melanomas metastasise to the bone and enhance osteoclast bone res
orption. We demonstrated that a 48-h-B16 melanoma cell conditioned media (B
16CM) induced osteoclastogenesis in mouse bone marrow cultures, without the
requirement of B16 cell-bone marrow cell co-culture. B16 cells transcripti
onally expressed detectable levels of TGF beta1, IL-6, M-CSF, GM-CSF and TN
F alpha mRNAs, albeit to a lower extent compared with levels in osteoblasts
, and failed to express PTHrP, OPGL, OPG and IL-1 beta. interestingly, B16C
M greatly upregulated IL-1 beta, IL-6 and GM-CSF, and modestly enhanced TNF
alpha and OPGL mRNA expression in osteoblasts, suggesting a potential indi
rect stimulation of osteoclastogenesis via the osteogenic lineage. B16CM ba
rely upregulated c-Fos, but strongly and time-dependently enhanced c-Src ex
pression in the total hone marrow cultures during osteoclast differentiatio
n. Moreover, c-Src expression was enhanced in differentiated and purified o
steoclast preparations to higher levels than in stromal cells. In conclusio
n. melanoma induces osteoclast generation with a paracrine mechanism indepe
ndent of cell-cell contact, specifically upregulating c-Src in osteoclasts
acid cytokine expression in osteoblasts. (C) 2001 Elsevier Science Ltd. All
rights reserved.