Melanoma cells stimulate osteoclastogenesis, c-Src expression and osteoblast cytokines.
Malignant melanomas metastasise to the bone and enhance osteoclast bone resorption. We demonstrated that a 48-h-B16 melanoma cell conditioned media (B16CM) induced osteoclastogenesis in mouse bone marrow cultures, without the requirement of B16 cell-bone marrow cell co-culture. B16 cells transcriptionally expressed detectable levels of TGFbeta1, IL-6, M-CSF, GM-CSF and TNFalpha mRNAs, albeit to a lower extent compared with levels in osteoblasts, and failed to express PTHrP, OPGL, OPG and IL-1beta. Interestingly, B16CM greatly upregulated IL-1beta, IL-6 and GM-CSF, and modestly enhanced TNFalpha and OPGL mRNA expression in osteoblasts, suggesting a potential indirect stimulation of osteoclastogenesis via the osteogenic lineage. B16CM barely upregulated c-Fos, but strongly and time-dependently enhanced c-Src expression in the total bone marrow cultures during osteoclast differentiation. Moreover, c-Src expression was enhanced in differentiated and purified osteoclast preparations to higher levels than in stromal cells. In conclusion, melanoma induces osteoclast generation with a paracrine mechanism independent of cell-cell contact, specifically upregulating c-Src in osteoclasts and cytokine expression in osteoblasts.
Perez
M
M
Istituto Dermopatico dell'Immacolata, 00167, Rome, Italy.
Migliaccio
S
S
Taranta
A
A
Festuccia
C
C
Orrù
L
L
Brama
M
M
Bologna
M
M
Faraggiana
T
T
Baron
R
R
Teti
A
A
D000818:Animals; D001862:Bone Resorption / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016391:Genes, src / Q000235:genetics*; D066298:In Vitro Techniques; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D016207:Cytokines; D012333:RNA, Messenger; D012334:RNA, Neoplasm