Inhibition of experimental metastasis with indomethacin: role of macrophages and natural killer cells.
The metastatic capacity of murine mammary tumor line 410.4 is greatly increased by treatment of the host with asialo-GM1 antiserum (5-fold), 2-chloroadenosine (4-fold) or k-carrageenan (2.5-fold). This suggests that both NK cells and macrophages contribute to control of metastatic dissemination. The metastatic potential of these cells is associated with the synthesis of high levels of prostaglandin E2 (PGE2) (1). When line 410.4 cells are cultured in vitro in the presence of the prostaglandin synthesis inhibitor indomethacin (INDO) 1 microM) their subsequent lung colonization ability (experimental metastasis) is reduced by 50-90% as compared to solvent-treated cells. The inhibitory effect of INDO is highly dependent on the presence of asGM1 positive cells, and is compromised to a lesser extent by treatments directed towards macrophages. The INDO-mediated inhibition is neither due to differential arrest of tumor cells in the lung nor does it appear to be due to shifts in the replication cycle.
Fulton
A M
AM
E. Walter Albachten Department of Immunology, Michigan Cancer Foundation, Detroit 48201.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015232:Dinoprostone; D005260:Female; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000276:immunology / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011458:Prostaglandins E / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D006028:Glycosphingolipids; D007106:Immune Sera; D011458:Prostaglandins E; D015762:2-Chloroadenosine; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D002351:Carrageenan; D000241:Adenosine; D015232:Dinoprostone; D007213:Indomethacin