Mechanisms of bone destruction in the development of skeletal metastases

Galasko, C. S. B.

doi:10.1038/263507a0

Cited by 266 publications

(88 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Melanoma cells also produce a soluble factor that stimulates osteoclast formation by a RANKL-independent mechanism. In early skeletal metastases where a relatively high macrophage: tumour cell ratio and large number of osteoclasts are typically found (Galasko, 1976;Bugelski et al, 1985), RANKL-dependent and RANKL-independent mechanism of pathological bone resorption are likely to play a role in the establishment of a metastatic malignant melanoma in bone.…”

Section: Discussionmentioning

confidence: 99%

Malignant melanoma and bone resorption

et al. 2006

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Malignant melanoma and bone resorption

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Prostaglandins and other lessclearly defined "tumour-associated" products may be involved in the establishment and growth of metastases in bone and possibly in other sites (Carter, 1978;Bennett, 1979). Prostaglandin E2 (PGE2) and some other prostanoids stimulate osteoclasts (Galasko, 1976;Carter, 1978;Bennett, 1979) and the recent observation of pronounced osteoclastic activity associated with squamous carcinomas of the head and neck invading bone (Carter & Tanner, 1979;Carter et al, 1980) prompted the present investigation.…”

mentioning

confidence: 98%

Prostaglandin-like material extracted from squamous carcinomas of the head and neck

Bennett¹,

Carter²,

Stamford³

et al. 1980

Br J Cancer

View full text Add to dashboard Cite

Summary.-Tumour-associated prostaglandin-like material, assessed by bioassay, has been examined in 37 patients with primary and metastatic squamous carcinomas of the head and neck, previously treated by radiotherapy and chemotherapy followed by radical surgery. High amounts of prostaglandin-like material were extracted from tumours excised within 3 months of radiotherapy and chemotherapy. These amounts correlated with necrosis, inflammation and fibrosis, but not with tumour site, size or degree of differentiation. Most of the prostaglandins formed by these treated tumours thus seem to be associated with host stromal and inflammatory cells, rather than the neoplastic cells. The possible roles of prostaglandins in facilitating the spread of squamous carcinomas are discussed.

show abstract

“…This is in accord with the report that in addition to osteolytic PGF and PGE produced by tumours there are other factors which are at least as important (Dowsett et al, 1976). Histological evidence suggests that bone invasion by metastatic tumour depends initially on osteoclastic activity and, in a second phase, on direct bone destruction by tumour cells (Galasko, 1976). …”

Section: 18) As the Number Of Patients Is Smallmentioning

confidence: 99%