title: Interactions of natural effector cells and prostaglandins in the control of metastasis.
abstract: The roles of prostaglandins and nonspecific immune effector cells were examined in the growth and metastasis of a series of murine mammary adenocarcinomas growing in BALB/c mice. The spontaneous metastasis of the highly metastatic tumor designated 410.4 was inhibited by oral administration of the prostaglandin synthesis inhibitor indomethacin (INDO), whereas treatment of mice with the interferon inducer polyinosinic-polycytidylic acid (poly I:C) delayed tumor growth but did not affect the rate of spontaneous metastasis. Lung colony formation was dramatically reduced by poly I:C treatment following iv tumor cell inoculation (experimental metastasis), whereas oral INDO had no significant effect. Suppression of natural killer cell activity with anti-asialo GM1 (asGM1) antibody increased lung colony-forming ability of mammary tumor lines with either high, moderate, or low metastatic capacity. Although pretreatment of the recipient with INDO did not alter the incidence of experimental metastasis, culture of the tumor cells with INDO (1 micron) prior to iv inoculation inhibited the appearance of lung colonies by greater than 90%. This beneficial effect was dependent on an asGM1-positive population. These results suggest that in this murine mammary tumor system, prostaglandin synthesis contributes to metastatic capacity and that the beneficial effects of INDO may be attributable, in part, to the enhancement of tumor cell sensitivity to natural cytotoxic effector mechanisms.
authors.forename: A M
authors.initials: AM
authors.lastname: Fulton
mesh_terms: D000818:Animals; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology*; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011453:Prostaglandins / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D007213:Indomethacin