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Malignant melanoma and bone resorption.
- Source :
-
British Journal of Cancer . 5/22/2006, Vol. 94 Issue 10, p1496-1503. 8p. 4 Black and White Photographs, 1 Chart, 3 Graphs. - Publication Year :
- 2006
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BONE metastasis
*MELANOMA
*BONE cancer
*BONE resorption
*OSTEOCLASTS
*CYTOKINES
*CANCER cells
*ANTINEOPLASTIC agents
*CARRIER proteins
*CELL culture
*CELL differentiation
*CELL receptors
*COMPARATIVE studies
*CULTURE media (Biology)
*FIBROBLASTS
*GLYCOPROTEINS
*INTERLEUKIN-1
*MACROPHAGES
*RESEARCH methodology
*MEDICAL cooperation
*MEMBRANE proteins
*METASTASIS
*POLYMERASE chain reaction
*RESEARCH
*SKIN tumors
*TUMOR necrosis factors
*EVALUATION research
*REVERSE transcriptase polymerase chain reaction
*MEMBRANE glycoproteins
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 94
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 20927907
- Full Text :
- https://doi.org/10.1038/sj.bjc.6603103