Patterns and mechanisms of bone invasion by squamous carcinomas of the head and neck

The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma

“…Before invasion of the mandible, SCCs in close proximity to bone initially induce deposition of new bone, especially on the periosteal surface. Two distinct types of invasion of the mandible by oral SCCs have been described (6,8,9). In the erosive pattern the tumor advances on a broad front separated from bone by a layer of connective tissue and osteoclasts are present in the region between bone and stromal tissue.…”

“…1D). Patients with advanced oral SCC have a high mortality, but treatment is complicated by the disruption of speech and swallowing after surgical resection (6)(7)(8)(9)(10)(11). It is generally agreed that patients with mandibular invasion should be treated surgically, although the extent of mandibular resection required remains controversial.…”

Macromolecular osteolytic factor synthesised by squamous carcinoma cell lines from the head and neck in vitro is interleukin 1

“…The initial stages of tumour-induced bone destruction are mediated by osteoclastic activity, whereas the later stages can involve direct invasion and destruction of the bone by tumour cells alone (Galasko & Bennett, 1976;Carter, 1985). There is much evidence that prostaglandins are synthesised by human carcinomas (Bennett et al, 1975;Dowsett et al, 1976;Tsao et al, 1981Tsao et al, , 1983 and, in view of their potent bone resorbing activity, notably PGE2 (Klein & Raisz, 1970), they have been considered prime candidates as osteolytic mediators.…”

“…The localised bone destruction frequently accompanying squamous cell carcinomas of the head and neck appears to be a two-stage process: the first phase characterised by osteoclastic resorption -presumably stimulated by tumour cell products, and a second phase of resorption by tumour cells themselves (Carter, 1985).…”

“…This co-eluted with activity in a preparation of ILl from rat peritoneal macrophage cultures. These results indicate that ILI is responsible for the prostaglandinindependent bone resorbing activity synthesised by these cells in vitro, and may contribute to the bone destruction associated with the tumour.Bone resorption is a common feature of malignancy and can occur as a consequence of malignant cell growth in or adjacent to bone, or at sites distant from the malignant cells.The localised bone destruction frequently accompanying squamous cell carcinomas of the head and neck appears to be a two-stage process: the first phase characterised by osteoclastic resorption -presumably stimulated by tumour cell products, and a second phase of resorption by tumour cells themselves (Carter, 1985).Since the demonstration of soluble bone resorbing activity produced by mouse fibrosarcoma in vitro (Goldhaber, 1960), tissue culture has been an important tool for investigating the mechanisms of tumour-induced bone resorption. Prostaglandins (PG), notably PGE2, have been considered prime candidates as local mediators of osteolysis since they are potent stimulators of oesteoclastic bone resorption (Klein & Raisz, 1970) and are synthesised in increased amounts by several tumours in animals, including fibrosarcoma in mice (Tashjian et al, 1972) the VX2 carcinoma in rabbits (Voelkel et al, 1975), and in man, including carcinoma of the breast (Bennett et al, 1975);Dowsett et al, 1976), and squamous carcinomas of the head and neck (Tsao et al, 1981).…”