Perspectives on polyhalogenated aromatic compounds.

Mechanisms of bone invasion by squamous carcinomas of the head and neck have, been investigated using fresh tumours and established tumour cell lines in an in vitro bone resorption assay with 45Ca-labelled mouse calvaria. Fresh tumours regularly resorb bone in vitro. Activity is consistently reduced by indomethacin. The tumours release E2 prostaglandins (PGE2) in amounts sufficient to account for-50% of the bone resorption observed. Small amounts of non-prostaglandin (indomethacin-resistant) osteolytic factors are also produced. Control non-neoplastic tissues show a variable capacity to resorb bone in vitro; PGE2 levels in these tissues may be related to their content of inflammatory cells. Tumour cell lines also resorb bone in vitro but, for most lines, activity is not significantly blocked by indomethacin and PGE2 levels are generally insufficient to account for the osteolysis observed. Non-prostaglandin bone resorbing factors thus predominate. It is concluded that most squamous cancers of the head and neck are osteolytic in vitro and release a mixture of prostaglandin and non-prostaglandin factors which stimulate osteoclastic bone resorption. These factors are derived from both neoplastic and stromal elements, and are "tumour-associated" rather than "tumour-specific". In vitro bone resorption and prostaglandin release does not correlate with pathological features of the tumour or with post-operative survival. Osteoclasts accumulate at sites of bone invasion by squamous carcinomas of the head and neck, and appear to play an important role in the destructive process (Carter, 1982). Prostaglandins are known stimulants of osteoclastic activity, and raised levels of extractable prostaglandin-like material were demonstrated by bioassay in a series of squamous cancers from the head and neck region (Bennett et al., 1980). Subsequent work showed that fresh tumour tissues and tumour cell lines were osteolytic in vitro and that bone resorption could be partly blocked by indomethacin (Tsao et al., 1981). These studies have been extended and information is now presented on the identification and quantitation of the prostaglandins involved and the contribution made by host tissues as a source of osteolytic factors. Observations on bone resorption by xenografts of squamous carcinomas have been reported separately (Tsao et al., 1983). Materials and methods Bone resorption assay The methods used were based on the procedure devised by Reynolds (1968) and have been fully described by us (Tsao et al., 1981). In brief, calvaria were dissected from 5 to 7 day old BALB/c mice previously injected with 45CaCl2, and cultured on metal grids in modified Bigger's medium, supplemented with …