thromboxane-b2 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

Individual prostanoids have distinct potencies in activating intracellular signaling pathways and regulating gene expression in osteoblastic cells. The E-series prostaglandins (PGs) are known to stimulate matrix metalloproteinase-1 (MMP-1) synthesis and secretion in certain rodent and human osteoblastic cells, yet the intracellular events involved remain unclear. To further characterize this response and its signal transduction pathway(s), we examined prostanoid-induced expression of the MMP-1 gene in the rat osteoblastic osteosarcoma cell line UMR 106-01. Northern blot analysis demonstrated that prostaglandin E2 (PGE2) and PGE1 were very potent stimulators (40-fold) of MMP-1 transcript abundance, PGF2 alpha and prostacyclin were weak stimulators (4-fold), and thromboxane-B2 had no effect. The marked increase in MMP-1 transcript abundance after PGE2 treatment was first detected at 2 h, became maximal at 4 h, and persisted beyond 24 h. This response was dose dependent and elicited maximal and half-maximal effects with concentrations of 10(-6) and 0.6 x 10(-7) M, respectively. Cycloheximide, a protein synthesis inhibitor, completely blocked this effect of PGE2, suggesting that the expression of other genes is required. Nuclear run-on experiments demonstrated that PGE2 rapidly activates MMP-1 gene transcription, with a maximal increase at 2-4 h. The second messenger analog, 8-bromo-cAMP, mimicked the effects of PGE2 by stimulating a dose-dependent increase in MMP-1 messenger RNA (mRNA) levels, with a maximal effect quantitatively similar to that observed with PGE2. Thus, in UMR 106-01 cells, different prostanoids have distinct potencies in stimulating MMP-1 mRNA abundance. Our data suggest that PGE2 stimulation of MMP-1 synthesis is due to activation of MMP-1 gene transcription and a subsequent marked increase in MMP-1 mRNA abundance. This effect is dependent on de novo protein synthesis and is mimicked by protein kinase-A activation.

Topics: Animals; Blotting, Northern; Bone Neoplasms; Collagenases; Cyclic AMP-Dependent Protein Kinases; Cycloheximide; Dinoprostone; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Enzymologic; Matrix Metalloproteinase 1; Osteosarcoma; Prostaglandins; Rats; RNA, Messenger; Thromboxane B2; Time Factors; Tumor Cells, Cultured

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

Topics: Adenylyl Cyclases; Animals; Cyclic AMP; Epoprostenol; Osteosarcoma; Prostaglandins; Prostaglandins E; Rats; Sarcoma, Experimental; Thromboxane B2; Thromboxanes