Malignant melanoma and bone resorption.

Journal article

The cellular and humoral mechanisms accounting for osteolysis in skeletal metastases of malignant melanoma are uncertain. Osteoclasts, the specialised multinucleated cells that carry out bone resorption, are derived from monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs) from metastatic (lymph node/skin) melanomas and cultured them in the presence and absence of osteoclastogenic cytokines and growth factors. The effect of tumour-derived fibroblasts and melanoma cells on osteoclast formation and resorption was also analysed. Melanoma TAMs (CD14+/CD51-) differentiated into osteoclasts (CD14-/CD51+) in the presence of receptor activator for nuclear factor kappaB ligand (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage-osteoclast differentiation also occurred via a RANKL-independent pathway when TAMs were cultured with tumour necrosis factor-alpha and interleukin (IL)-1alpha. RT-PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL messenger RNA and the conditioned medium of cultured melanoma fibroblasts was found to be capable of inducing osteoclast formation in the absence of RANKL; this effect was inhibited by the addition of osteoprotegerin (OPG). We also found that cultured human SK-Mel-29 melanoma cells produce a soluble factor that induces osteoclast differentiation; this effect was not inhibited by OPG. Our findings indicate that TAMs in metastatic melanomas can differentiate into osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce osteoclast formation by RANKL-dependent and RANKL-independent mechanisms, respectively.

Authors: Lau, Y; Sabokbar, A; Giele, H; Cerundolo, V; Hofstetter, W

• Publication status: Published
• Journal: British journal of cancer
• Volume: 94
• Issue: 10
• Pages: 1496-1503
• Publication date: 2006-05-01
• DOI: 10.1038/sj.bjc.6603103
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English
• Keywords: Membrane Glycoproteins; Female; Glycoproteins; Culture Media, Conditioned; Antineoplastic Agents; Macrophages; Fibroblasts; Tumor Necrosis Factor-alpha; Interleukin-1; Osteoprotegerin; Skin Neoplasms; Cells, Cultured; Receptor Activator of Nuclear Factor-kappa B; Middle Aged; Aged, 80 and over; Male; Receptors, Tumor Necrosis Factor; Cell Differentiation; Aged; Osteoclasts; Humans; Receptors, Cytoplasmic and Nuclear; Bone Resorption; Lymphatic Metastasis; Reverse Transcriptase Polymerase Chain Reaction; Carrier Proteins; Osteolysis; Melanoma; RANK Ligand