6-ketoprostaglandin-f1-alpha and Osteosarcoma

Several reports have shown peritumoral edema accompanying primary bone tumors demonstrated by magnetic resonance imaging (MRI). However, the mechanism of this inflammatory reaction is still unclear. The authors postulated that the reaction was caused by some chemical mediators including prostanoids, because several investigators have observed that some types of bone tumors synthesize prostanoids. Therefore, the authors compared MRI findings and tumor prostaglandin (PG) levels.. The subjects were 29 patients with primary bone tumor or tumor-like conditions: chondroblastoma (n = 5); chondrosarcoma, including rare variants (n = 8); giant cell tumor (n = 6); osteochondroma (n = 5); osteoblastoma (n = 2); Ewing's sarcoma (n = 2); and eosinophilic granuloma (n = 1). T1- and T2-weighted spin echo images were obtained in all but one patient before surgery. The tumor concentration of prostaglandin E2, 6-keto-PGF1 alpha, and thromboxane B2 were measured by radioimmunoassay.. MRI distinctly showed bone marrow edema in 9 and soft tissue edema in 12 of the 28 patients examined. These findings were significantly correlated with the PG levels. Moreover, the PG levels were correlated with the histologic classifications (P < 0.001). In particular, the chondroblastomas showed prominent concentrations of PGs compared with other cartilaginous tumors or giant cell tumors.. Although peritumoral edema accompanying benign and malignant bone tumors is not necessarily related to one single pathophysiologic mechanism, these results suggest that PG production was an important cause of the inflammatory reaction that was revealed by MRI. Recognition of this phenomenon is advantageous not only for strict diagnostic purposes but also for understanding the characteristic features of individual primary bone tumors.

Topics: 6-Ketoprostaglandin F1 alpha; Bone Neoplasms; Chondroblastoma; Dinoprostone; Edema; Eosinophilic Granuloma; Humans; Magnetic Resonance Imaging; Neoplasm Proteins; Osteoblastoma; Osteosarcoma; Thromboxane B2

The effects of interleukin-1 alpha (IL-1 alpha) on arachidonic acid (AA) metabolism were studied in the human osteosarcoma cell lines, G292 and SaOS-2. The cells were prelabeled with 3H-arachidonic acid. Radiolabeled metabolites were measured by reversed-phase high-pressure liquid chromatography with a radioactive detector. Indomethacin inhibited prostaglandin E2 (PGE2) production without affecting lipoxygenase (LO) products in G292 cells. In the G292 cells, IL-1 alpha (50 U/ml) induced a 10-fold increase in PGE2 production at all the incubation times tested, and a significant two-fold increase in 5 hydroxyeicosatetraenoic acid (HETE) formation after 48 h. These effects were not seen in SaOS-2 cells under identical conditions. These results suggest that, although some osteosarcomal cell lines may not respond directly to IL-1 with effects on AA metabolism, the mechanism of its action in others may involve modulation of both cyclooxygenase (CO) and LO pathways.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Dinoprostone; Humans; Hydroxyeicosatetraenoic Acids; Indomethacin; Interleukin-1; Leukotriene B4; Lipoxygenase; Osteoblasts; Osteosarcoma; Tumor Cells, Cultured

The effect of prostaglandins (PG) on free cytosolic calcium concentrations [( Ca2+]i) and cAMP levels was studied in the osteosarcoma cell line UMR-106. PGF2 alpha and PGE2, but not 6-keto-PGF1 alpha, induced an increase in [Ca2+]i which was mainly due to Ca2+ release from intracellular stores. The EC50 for PGF2 alpha was approximately 7 nM, whereas that for PGE2 was approximately 1.8 microM. Maximal doses of PGF2 alpha increased [Ca2+]i to higher levels than PGE2. Both active PGs also stimulated phosphatidylinositol turnover in UMR-106 cells. The effects of the two PGs were independent of each other and appear to involve separate receptors for each PG. PGE2 was a very potent stimulator of cAMP production and increased cAMP by approximately 80-fold with an EC50 of 0.073 microM. PGF2 alpha was a very poor stimulator of cAMP production; 25 microM PGF2 alpha increased cAMP by 5-fold. The increase in cellular cAMP levels activated a plasma membrane Ca2+ channel which resulted in a secondary, slow increase in [Ca2+]i. High concentrations of both PGs (10-50 microM) inhibited this channel independent of their effect on cAMP levels. Pretreatment of the cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate inhibited the PG-mediated increase in phosphatidylinositol turnover and the increase in [Ca2+]i. However, pretreatment with 12-O-tetradecanoyl-13-acetate had no effect on the PGE2-mediated increase in cAMP. The latter finding, together with the dose responses for PGE2-mediated increases in [Ca2+]i and cAMP levels, suggests the presence of two subclasses of PGE2 receptors: one coupled to adenylate cyclase and the other to phospholipase C. With respect to osteoblast function, the cAMP signaling system is antiproliferative, whereas the Ca2+ messenger system, although having no proliferative effect by itself, tempers cAMP's antiproliferative effect.

Topics: 6-Ketoprostaglandin F1 alpha; Calcium; Cell Line; Cyclic AMP; Cytosol; Dinoprost; Dinoprostone; Ethers; Ionomycin; Kinetics; Osteosarcoma; Prostaglandins; Prostaglandins E; Prostaglandins F

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Bone Neoplasms; Female; Humans; Male; Osteosarcoma; Reference Values; Sarcoma, Ewing; Sarcoma, Synovial; Thromboxane B2; Thromboxanes

The metabolism of arachidonic acid to its cyclo-oxygenase products was studied in monolayer cultures of osteoblast-rich rat calvarial cells and of clonal cell lines from a rat osteogenic sarcoma, enriched in the osteoblast phenotype. Prostanoids were measured by radioimmunoassay after extraction of media and fractionation by high pressure liquid chromatography. In both normal and malignant osteoblasts the major cyclooxygenase product was 6-oxo-prostaglandin F1 alpha, the hydration product of prostacyclin, with lesser amounts of prostaglandin E2 and prostaglandin F2 alpha. No significant thromboxane B2 was detected. Prostaglandins are thought to have a local role in the regulation of bone resorption. These results point to the possible importance of prostacyclin either in bone resorption or in some other local function, e.g., regulation of bone blood flow.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Cell Line; Cells, Cultured; Dinoprost; Dinoprostone; Osteoblasts; Osteosarcoma; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Thromboxane B2