Polyamine deprivation stimulates natural killer cell activity in cancerous mice.
It has recently been established that the total blockade of all endogenous and exogenous sources of polyamines by a drug containing polyamine deficient chow (DC-PDC+) could inhibit tumor growth in vivo and increase the antitumoral efficacy of chemotherapy drugs. We show here that polyamine deprivation obtained with DC-PDC+ not only influences tumor development via reduction of polyamine concentrations in the tumor itself but, in addition, stimulates cells of the non-specific immune system specialized in tumor cell killing. We report that mice grafted with the 3LL carcinoma present a dramatic decrease in the cytotoxic activity of their natural killer (NK) cells. When these animals are treated with DC-PDC+, their NK cell activity is completely restored to normal values. Normalization of leucocyte number and differential count was observed as well. With respect to the different components of the DC-PDC+, it was observed that the endogenous and exogenous sources of polyamines have a different degree of impact on tumor development. For example, when only polyamines from digestive sources are deprived, a weak but significant improvement in NK activity and antitumoral effects were observed, without affecting intra-tumoral polyamine concentrations. We conclude that polyamines, secreted by the tumor itself as well as absorbed through the gastrointestinal tract, could now be considered not only as autocrine growth factors but also as natural immunosuppressive factors.
Chamaillard
L
L
Laboratoire de Biologie Cellulaire, Centre Hospitalier Universitaire de Rennes, France.
Quemener
V
V
Havouis
R
R
Moulinoux
J P
JP
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004032:Diet; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009355:Neomycin / Q000494:pharmacology; D011073:Polyamines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D012016:Reference Values
D011073:Polyamines; D008795:Metronidazole; C044445:MDL 72527; D009355:Neomycin; D011700:Putrescine; D000518:Eflornithine