Inability of anti-asialo-GM1 and 2-chloroadenosine to abrogate maleic anhydride-divinyl ether-induced resistance against experimental murine lung carcinoma metastases.
Both macrophages and natural killer cells have been implicated in the antimetastatic activity of maleic anhydride-divinyl ether (MVE-5). In the present study, we attempted to utilize anti-asialo-GM1 antibody and 2-chloroadenosine, agents that kill natural killer (NK) cells and macrophages, respectively, to determine the relative contribution of each effector cell type to the overall host defense. These agents were tested in the M109 lung metastasis model in syngeneic BALB/c mice, and the cytotoxic activities of both peritoneal macrophages and splenic NK cells were followed. The most profound antitumor effect was observed when MVE-5 was given before rather than after i.v. tumor inoculation. Treatment i.p. with MVE-5 at 20 mg/kg produced greater than 98% inhibition of subsequent lung metastases when given 2 days prior to tumor. Anti-asialo-GM1 antibody (25 mg/kg, i.p.) and 2-chloroadenosine (50 mg/kg, i.p.) were administered concurrently with MVE-5. Although each agent exhibited greater selectivity for its respective target, the early (Day 2) inhibitory response was nonspecific. By Day 5 after MVE-5 treatment, 2-chloroadenosine only inhibited macrophage tumoricidal activity, and conversely, anti-asialo-GM1 antibody only inhibited NK reactivity. Despite the ability of these agents to increase survival of metastases in control animals, they only slightly abrogated the antimetastatic activity of MVE-5. Our data suggest that caution should be exercised in using these agents to discriminate macrophage and NK responses.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000937:Antigen-Antibody Reactions; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007157:Immunologic Surveillance / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000556:secondary; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000494:pharmacology*; D011713:Pyran Copolymer / Q000494:pharmacology*
D000906:Antibodies; D006028:Glycosphingolipids; D011108:Polymers; D015762:2-Chloroadenosine; D011713:Pyran Copolymer; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D000241:Adenosine