dinoprost and Bone-Neoplasms

Modulation of endothelin (ET-1)-induced [Ca(2+)](i)transients and receptor expression by parathyroid hormone (PTH) was studied in UMR-106 osteoblastic osteosarcoma cells. Ca(2+)signaling was assessed with Fura-2, and ET receptor mRNA expression was determined using ET(A)- and ET(B)-specific primers and RT-PCR amplification. ET-1 binding in UMR-106 cell membranes was also measured. PTH pretreatment for 8 h decreased the [Ca(2+)](i)transients elicited by ET-1 and by the ET(B)-selective agonist sarafotoxin 6c (S6c). When ET(B)receptors were desensitized by pretreatment with S6c or blocked with the ET(B)-selective antagonist BQ-788, the remaining ET(A)component of the signal was also decreased by PTH pretreatment. In contrast, [Ca(2+)](i)transients elicited by PGF(2alpha)and ionomycin were increased following PTH pretreatment, indicating that the effect of PTH to decrease ET-1-stimulated transients was selective. PTH pretreatment also decreased [(125)I]ET-1 binding and ET(A)and ET(B)mRNA, with maximal effects at approximately 8 h. ET-1 was not detectable in medium from either control or PTH treated UMR-106 cultures, suggesting that the decreased expression of ET receptors was not due to enhanced ET production and subsequent homologous desensitization. The downregulation of ET receptors in osteoblasts by PTH pretreatment may serve as a homeostatic mechanism in bone.

Topics: Bone Neoplasms; Calcium Signaling; Cell Membrane; Dinoprost; Down-Regulation; Endothelin Receptor Antagonists; Endothelin-1; Ionomycin; Ionophores; Oligopeptides; Osteoblasts; Osteosarcoma; Parathyroid Hormone; Piperidines; Protein Isoforms; Receptors, Endothelin; RNA, Messenger; Tumor Cells, Cultured; Viper Venoms

Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E2, a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125I-labelled EGF: the apparent dissociation constant was approximately 4-10 X 10(-10) M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE2 into medium, while no significant amount of PGE2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGF2 alpha, PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 or G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE2-mediated process in human osseous tissues.

Topics: Adult; Alprostadil; Animals; Bone Neoplasms; Bone Resorption; Calcitonin; Cell Line; Child; Cyclic AMP; Dinoprost; Dinoprostone; ErbB Receptors; Female; Giant Cell Tumors; Humans; Indomethacin; Male; Mice; Osteosarcoma; Parathyroid Hormone; Prostaglandins E; Prostaglandins F; Receptors, Cell Surface

PGE2 overproduction by a nephroblastoma associated with hypercalcemia was clearly demonstrated in a 2-month-old girl. Compared with normal tissue, tumor showed greater phospholipase A2 and PGE2 synthetase activities but metabolized PGE2 at a faster rate. Of the enzymes involved in PGE2 synthesis, those which transform arachidonic acid into PGE2 seem to be more active.

Topics: Bone Neoplasms; Dinoprost; Dinoprostone; Female; Humans; Hypercalcemia; Infant; Kidney Neoplasms; Phospholipases A; Phospholipases A2; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Wilms Tumor

Patterns and mechanisms of local bone invasion by squamous carcinomas of the head and neck have been investigated. Detailed surgical pathology has shown that these tumors invade contiguous skeletal or metaplastic bone principally through an indirect process; the normal bone resorbing cells of the host (osteoclasts) are activated and erode bone in front of the advancing tumor edge. Tumor cells take over the destructive process when the osteoclast response has waned. These morphologic patterns have been reproduced in an in vitro model where calcium-45-labelled mouse calvaria, cocultured with a tumor for 3 days, are resorbed by osteoclasts. Freshly excised tumors, established tumor cell lines, and tumor xenografts release osteolysins in vitro which act as osteoclastic stimulants. They include both prostaglandins E2 and F2 alpha, and nonprostaglandin factors, and are derived from tumor cells and from the associated host stroma. Virtually all the tumors examined released osteolysins and resorbed bone in vitro independent of their site, size, degree of differentiation, and the presence or absence of clinical bone invasion.

Topics: Bone Neoplasms; Calcium; Carcinoma, Squamous Cell; Cell Line; Cells, Cultured; Dinoprost; Dinoprostone; Head and Neck Neoplasms; Humans; In Vitro Techniques; Laryngeal Neoplasms; Osteolysis; Prostaglandins E; Prostaglandins F