Further observations on mechanisms of bone destruction by squamous carcinomas of the head and neck: the role of host stroma.
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 approximately 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.
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000503:physiopathology*; D002460:Cell Line; D003470:Culture Media; D046508:Culture Techniques; D015237:Dinoprost; D015232:Dinoprostone; D005347:Fibroblasts / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D012867:Skin / Q000378:metabolism
D003470:Culture Media; D011458:Prostaglandins E; D011460:Prostaglandins F; D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin