Prostaglandins and metastasis.
The data presented suggest that F1 and F10 cells display an inverse relationship between their levels of metastasis and prostaglandin D2 production. Prostaglandin D2 was able to reduce in vitro aggregation of platelets from C57 black mice. Other prostaglandins that decreased platelet aggregation such as prostacyclin also reduced the metastatic rate. Prostaglandin D2 also reduced macrophage cytotoxicity for B16 target cells in vitro. Interferons stimulated prostaglandin D2 synthesis in F10 cells and reduced lung metastasis. F10 metastasis was not blocked by interferon to the same extent by in vivo treatment as it had been in vitro, suggesting that interferons and other modulators of cell function have broader activity in vivo than simply increasing the level of prostaglandins being produced by metastatic cells. Metastasis can therefore be viewed as being modulated in vivo by several mechanisms that may include platelet aggregation and elimination of metastasized cells by host defenses such as macrophages. Prostaglandins and other naturally occurring modulators of host resistance, such as interferons, appear to affect the metastatic rate of tumor cells. Although prostaglandin D2 is not a common major AA product of most cells and therefore may not operate in all cell systems, the B16 cells may provide a system to address the importance of these mediators and mechanisms in the metastatic process.
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D007113:Immunity, Innate; D007213:Indomethacin / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010974:Platelet Aggregation; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000096:biosynthesis*
D011457:Prostaglandins D; D007372:Interferons; D015230:Prostaglandin D2; D007213:Indomethacin