Melanoma cells stimulate osteoclastogenesis, c-Src expression and osteoblast cytokines

Perez, Marie; Migliaccio, Silvia; Taranta, Anna; Festuccia, Claudio; Orrù, Luigi; Brama, Marina; Bologna, Mauro; Faraggiana, Tullio; Baron, Roland; Teti, Anna

doi:10.1016/s0959-8049(00)00436-6

Cited by 25 publications

(26 citation statements)

References 43 publications

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“…Bone is one of the three tissues most commonly affected by metastasis in human cancers (Perez et al, 2001). We asked whether TIMP-3 loss affected bone metastasis.…”

Section: Resultsmentioning

confidence: 99%

“…Macrophages belong to the monocytic lineage, which is also responsible for generating osteoclast. Osteoclasts are important mediators of osteolysis and can be activated by B16 melanoma cells (Perez et al, 2001;Mundy, 2002). We determined whether the higher level of osteolysis in B16F10-bearing timp-3 À/À bones was due to increased osteoclast population.…”

Section: Enhanced Metastatic Dissemination To Multiple Organs W Cruz-mentioning

confidence: 99%

“…Proteolytic remodeling of the extracellular matrix (ECM) facilitates multiple stages of cancer dissemination including tumor angiogenesis, invasion, migration, extravasation and colonization of secondary site (Chang and Werb, 2001). The common sites of metastasis for solid tumors are the lung, liver, bone and brain, whereas lymphomas frequently affect the kidney (Urban and Fishman, 2000;Perez et al, 2001). These tissues have specific morphology, cellular and ECM composition, and levels of growth factors and cytokines, and provide a distinct 'soil' for the metastatic cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3−/− mice

et al. 2006

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Identifying versatile inhibitors of metastasis that operate in multiple sites against distinct cancer cell types is important for designing novel therapeutics for metastasis. We show that multiple tissues of timp-3 À/À mice are more susceptible to metastatic colonization. Overall, a 5-14-fold increase in liver and kidney colonization occurred by EL-4 lymphoma cells, and a twofold increase upon targeting B16F10 melanoma cells to the bone or lung of timp-3 À/À mice. There was a general lack of macrophage or neutrophil localization to metastases in the liver, kidney and lung, and of osteoclasts to bone in both genotypes. Analysis of lung showed that proliferation or angiogenesis were unaltered within the metastatic colonies. Lung-trap assays revealed that initial tumor cell trapping was similar in the lung vasculature of timp-3 À/À and wild-type mice. However, more tumor cells were found in timp-3 À/À lungs at 48 and 96 h after tumor cell injection indicating more efficient extravasation and initial proliferation. Activation of pro-MMP-2 was greater in timp-3 À/À lungs at these time points. These data demonstrate TIMP-3 functions to inhibit metastatic dissemination of diverse cancer cells to multiple organs. TIMP-3 regulates MMP-2 activation to limit tumor cell extravasation and subsequent colonization of the lung, without augmenting inflammatory cell response.

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“…Bone is one of the three tissues most commonly affected by metastasis in human cancers (Perez et al, 2001). We asked whether TIMP-3 loss affected bone metastasis.…”

Section: Resultsmentioning

confidence: 99%

Section: Enhanced Metastatic Dissemination To Multiple Organs W Cruz-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3−/− mice

et al. 2006

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“…Melanoma cells are known to produce M-CSF in vitro (Perez et al, 2001, Varney et al, 2005. As some fibroblast populations are known to express RANKL and OPG, we investigated whether fibroblasts derived from secondary melanomas expressed these osteoclastogenic factors and were capable of supporting osteoclast formation.…”

Section: Discussionmentioning

confidence: 99%

“…Melanoma cells have previously been shown to stimulate the recruitment and activation of osteoclasts that carry out malignant bone resorption (Clohisy et al, 1996). Melanoma cells release a number of osteoclastogenic factors including TGF-b, IL-6, M-CSF, GM-CSF and TNF-a (Perez et al, 2001); these cells also upregulate osteoblast expression of factors known to stimulate RANKLdependent osteoclastogenesis. Melanoma cells, however, have not been shown to express RANKL (Chikatsu et al, 2000), and we did not identify RANKL mRNA in SK-Mel-29 human melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Malignant melanoma and bone resorption

et al. 2006

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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 þ /CD51À) differentiated into osteoclasts (CD14À/CD51 þ ) in the presence of receptor activator for nuclear factor kB 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-a and interleukin (IL)-1a. 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.

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Murine osteoclastogenesis suppression using conditioned media produced by melanoma or activated and non‐activated Jurkat‐E6 cells

Mambelli‐Lisboa

Frare

Costa-Neves

et al. 2020

Cell Biology International

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Conditioned medium (CM) (cell secretome) is a cocktail of growth factors, cytokines, and other soluble mediators secreted by cells into a culture medium. These growth factors are fundamental in many cellular processes such as cell growth, differentiation, and others and the composition of these factors is individual for each cell type. Osteoclasts are large multinucleated cells that are responsible for bone resorption. Immune and cancer cells are known to produce different growth factors, which are able to induce or inhibit osteoclast differentiation. Herein, we evaluated the effect of CM obtained from the supernatant of activated and non-activated Jukart-E6 cells, as well as from one murine (B16-F10) and one human melanoma cell line (SKMEL28). To induce osteoclast differentiation, murine bone marrow mononuclear cells were cultured in the presence and absence of differentiation factors (DF), such as macrophage colony-stimulating factor, prostaglandin E2, receptor activator of nuclear factor-κB ligand, and CM. We measured the concentration of interleukin 6, tumor necrosis factor-α and interferon γ (IFN-γ) in CM that can inhibit or induce osteoclastogenesis. Our study demonstrated that CM obtained from each cell line suppresses or inhibits osteoclasts formation at early and intermediate stages of differentiation in the absence or presence of DF. CM obtained from activated Jurkat-E6 cells demonstrates a stronger effect when compared with CM from naïve Jurkat-E6 cells or human and murine melanoma cells. Moreover, CM obtained from activated Jurkat-E6 cells shows higher secretion of IFN-γ, which is an inhibitor of osteoclastogenesis, in comparison with CM obtained from the three other cell lines. On the other hand, CM derived from B16-F10 cells showed a smaller inhibitory effect when compared with CM derived from the other cells. myristate acetate; RANK, receptor activator of nuclear factor kappa-B; RANKL, receptor activator of nuclear factor kappa-B ligand; RPMI, Roswell Park Memorial Institute Medium; TMB, 3,3′,5,5′-tetramethylbenzidine liquid substrate system; TNF-α, tumor necrosis factor-α; TRAF 6, TNF receptorassociated factor 6; TRAP, tartrate-resistant acid phosphatase; α-MEM, α-minimum essential medium.Nicole C. Mambelli-Lisboa and Eduardo O. Frare contributed equally to this work.Osteoclastogenesis suppression using conditioned media N. C. Mambelli-Lisboa et al.

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Melanoma cells stimulate osteoclastogenesis, c-Src expression and osteoblast cytokines

Cited by 25 publications

References 43 publications

Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3−/− mice

Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3−/− mice

Malignant melanoma and bone resorption

Murine osteoclastogenesis suppression using conditioned media produced by melanoma or activated and non‐activated Jurkat‐E6 cells

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