Modulation of tumor cell motility by prostaglandins and inhibitors of prostaglandin synthesis.
15-Methyl-prostaglandin E1 (15-M-PGE1), a synthetic stable, prostaglandin E1 analogue was examined for ability to inhibit motility in a line of murine tumor cells. Inhibition of random motility and motility stimulated by 12-O-tetradecanoyl phorbol acetate was seen at concentrations of 15-M-PGE1 as low as 1 microM. Inhibition of laminin-stimulated motility was observed with 10 microM 15-M-PGE1. The murine tumor cells used in this study produced high levels of prostaglandins. When the cells were treated with either indomethacin or ibuprofen, prostaglandin levels (measured as prostaglandin E2 by radioimmunoassay) were reduced by greater than 95% without a corresponding increase in lipoxygenase products. When indomethacin or ibuprofen-treated cells were compared to control cells in regards to motility, they were more active. These studies show that E-series prostaglandins can modulate motility in the murine fibrosarcoma cells and suggest that the production of endogenous cyclooxygenase metabolites by the murine tumor cells may regulate, at least in part, the responsiveness of the cells to stimulation.
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Fligiel
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Varani
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D000818:Animals; D001101:Arbaprostil / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D015232:Dinoprostone; D005354:Fibrosarcoma / Q000473:pathology*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis; D013189:SRS-A / Q000378:metabolism
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D013189:SRS-A; D015232:Dinoprostone; D001101:Arbaprostil; D007052:Ibuprofen; D007213:Indomethacin