Human tumour-associated macrophages differentiate into osteoclastic bone-resorbing cells

Quinn, J; McGee, J O; Athanasou, Nicholas A.

doi:10.1002/(sici)1096-9896(199801)184:1<31::aid-path962>3.0.co;2-v

Cited by 38 publications

(32 citation statements)

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“…The extent of lacunar resorption was measured using an image analysis software (Adobe Photoshop, USA) as previously described (Quinn et al, 1998) and expressed as the mean percentage of surface area resorbed7standard error of mean (s.e.m.). In order to minimise the effect of batch-to-batch variation of PBMCs, all resorption data were normalised and expressed relative to the response obtained in PBMC cultures incubated with 25 ng ml À1 M-CSF and 30 ng ml À1 RANKL (positive control).…”

Section: Discussionmentioning

confidence: 99%

“…Functional evidence of TAM-osteoclast formation was determined by a lacunar resorption assay system using cell cultures on dentine slices (Quinn et al, 1998). After 21 days incubation, the cells were removed from the dentine slices by treatment with 1 M ammonium hydroxide.…”

Section: Cytochemical and Functional Assessment Of Osteoclast Formationmentioning

confidence: 99%

“…It has been shown that tumourassociated macrophages (TAMs) are capable of osteoclast differentiation when these mononuclear phagocytes are co-cultured with bone-derived stromal cells (Quinn et al, 1998). In this study, our aim has been to determine the cellular mechanisms of tumour osteolysis associated with metastatic melanoma.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Cytochemical and Functional Assessment Of Osteoclast Formationmentioning

confidence: 99%

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Malignant melanoma and bone resorption

et al. 2006

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“…1,2 Osteoclasts and macrophages are known to have several morphological, cytochemical, and functional characteristics in common, and are derived from the same committed population of hematopoietic precursors. 3 In vitro studies have shown that osteoclasts in both mouse and humans may form directly from precursor cell populations of monocytes and macrophages.…”

Section: Introductionmentioning

confidence: 99%

Decoy receptor 3 (DcR3) induces osteoclast formation from monocyte/macrophage lineage precursor cells

Yang

Wang

Hsieh³

et al. 2004

Cell Death Differ

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Recent evidence indicates that the decoy receptor 3 (DcR3) of the TNF receptor superfamily, which initially though prevents cytokine responses of FasL, LIGHT and TL1A by binding and neutralization, can modulate monocyte function through reverse signaling. We show in this work that DcR3 can induce osteoclast formation from human monocytes, murine RAW264.7 macrophages, and bone marrow cells. DcR3-differentiated cells exhibit characteristics unique for osteoclasts, including polynuclear giant morphology, bone resorption, TRAP, CD51/61, and MMP-9 expression. Consistent with the abrogation of osteoclastogenic effect of DcR3 by TNFRFc, DcR3 treatment can induce osteoclastogenic cytokine TNF-a release through ERK and p38 MAPK signaling pathways. We conclude that DcR3 via coupling reverse signaling of ERK and p38 MAPK and stimulating TNF-a synthesis is a critical regulator of osteoclast formation. This action of DcR3 might play an important role in significant osteoclastic activity in osteolytic bone metastases.

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“…In both mouse and man, mononuclear osteoclast precursors circulate in the monocyte fraction and express a monocyte/macrophage rather than an osteoclast phenotype (Udagawa et al, 1990;Quinn et al, 1996;Fujikawa et al, 1996). Osteoclast differentiation from these circulating precursors requires the presence of M-CSF and involves a receptor-ligand interaction with osteoblasts which express a membrane-bound osteoclast differentiation factor (ODF) Yasuda et al, 1998).In previous studies we have shown that tumour-associated macrophages (TAMs) isolated from primary human breast and mouse mammary carcinomas, when cocultured with bone-derived stromal cells in the presence of 1,25(OH) 2 D 3 and M-CSF, are able to differentiate into multinucleated osteoclasts that are capable of extensive lacunar bone resorption (Quinn et al, 1994(Quinn et al, , 1998. This finding is of interest with regard to the pathogenesis of tumour osteolysis in breast cancer as, in addition to an increase in osteoclast number, a prominent macrophage infiltrate is commonly found in metastatic breast carcinomas (Bugelski et al, 1987;Van Ravenswaay Claasen et al, 1992).…”

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Cellular mechanisms of bone resorption in breast carcinoma

et al. 2001

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Bone destruction is a major complication of advanced malignant disease. It causes bone pain, pathological fracture and hypercalcaemia. Tumour-associated osteolysis and hypercalcaemia is seen in association with haematological malignancies (e.g. myeloma, lymphoma) and solid tumours, mainly carcinomas, where it may occur both in the presence (e.g. cancer of the lung, breast, thyroid, kidney, etc.) and absence (e.g. cancer of the lung, breast, head and neck, kidney, ovary, etc.) of bone metastases (Mundy, 1991;Dodwell, 1992). Bone is one of the commonest sites of metastasis in breast cancer and hypercalcaemia is seen in about one half of patients with clinical evidence of breast carcinoma.The cellular and molecular mechanisms that account for the bone destruction and consequent hypercalcaemia which occurs in patients with advanced malignant disease are poorly understood. Osteoclasts, multinucleated cells which form part of the mononuclear phagocyte system (Athanasou, 1996), effect the bone resorption in patients with skeletal metastasis (Galasko, 1976;Taube et al, 1994). Osteoclasts are formed by fusion of circulating mononuclear precursors cells of haematopoietic origin. In vitro studies have defined the ontogeny of the osteoclast and characterized the essential cellular and humoral factors which are required for osteoclast differentiation from haematopoietic and circulating osteoclast precursors. In both mouse and man, mononuclear osteoclast precursors circulate in the monocyte fraction and express a monocyte/macrophage rather than an osteoclast phenotype (Udagawa et al, 1990;Quinn et al, 1996;Fujikawa et al, 1996). Osteoclast differentiation from these circulating precursors requires the presence of M-CSF and involves a receptor-ligand interaction with osteoblasts which express a membrane-bound osteoclast differentiation factor (ODF) Yasuda et al, 1998).In previous studies we have shown that tumour-associated macrophages (TAMs) isolated from primary human breast and mouse mammary carcinomas, when cocultured with bone-derived stromal cells in the presence of 1,25(OH) 2 D 3 and M-CSF, are able to differentiate into multinucleated osteoclasts that are capable of extensive lacunar bone resorption (Quinn et al, 1994(Quinn et al, , 1998. This finding is of interest with regard to the pathogenesis of tumour osteolysis in breast cancer as, in addition to an increase in osteoclast number, a prominent macrophage infiltrate is commonly found in metastatic breast carcinomas (Bugelski et al, 1987;Van Ravenswaay Claasen et al, 1992). Moreover, osteoclasts are required for growth of breast cancer metastases in bone and tumour osteolysis involves recruitment of osteoclast precursors and activation of mature osteoclasts (Clohisy et al, 1996a(Clohisy et al, , 1996bClohisy and Ramnaraine, 1998).In this study, our aim has been to analyse the cellular mechanisms of bone resorption in breast cancer. As TAMs in metastases of breast cancer are derived from circulating monocytes (Mantovani et al, 1992), we have sought to determine wheth...

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Human tumour-associated macrophages differentiate into osteoclastic bone-resorbing cells

Abstract: Aldehydes react with silyl ethers or the corresponding alcohols and allylsilanes in the presence of catalytic amounts of 2,4‐dinitrobenzenesulfonic acid (DNBA) to provide a wide range of homoallylic ethers in moderate to high yields.

Cited by 38 publications

References 35 publications

Malignant melanoma and bone resorption

Malignant melanoma and bone resorption

Decoy receptor 3 (DcR3) induces osteoclast formation from monocyte/macrophage lineage precursor cells

Cellular mechanisms of bone resorption in breast carcinoma

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