[To stimulate or to inhibit nitric oxide production in mammary tumors?].
NO is a molecule produced in different amounts by two types of enzymes, constitutive NO-synthases and inducible NO-synthase, the last one produce large amount of NO. In tumor outcome, its role may be either beneficial or detrimental due to its actions in the different steps of tumor growth and metastasis. This review deals with mammary tumors and the mechanisms lying behind NO effects. In human patients, increased amounts of NO were evidenced in blood, linked with the presence and activity of NO-synthase in breast tumors. Non-unequivocal correlations were established with tumor grade, invasiveness and metastatic potential. Studies in animal models have given hints to explain these discrepancies by the type of the involved NO-synthase, the amount of NO it produces, and its belonging to tumoral or stromal cells. Indeed, it was recently shown that NO produced by tumor cells inhibits, while NO produced by stromal cells facilitates tumor growth, at least in the model which was studied. On the one hand, NO toxicity against tumor cells is a well known phenomenon, but on the other hand, NO may promote tumor invasiveness due to its effect on extracellular matrix, and to its angiogenetic properties. So the role of NO in mammary tumor outcome is not clear-cut, and, at the present time, it cannot be ascribed a pronostic value in breast tumor. However, researches aimed at managing tumor cells to produce NO sufficient to induce their death may be fruitful since, be tumor targeting successful, no general toxicity would be encountered.
Gauthier
Nolwenn
N
EPHE/Inserm, Laboratoire d'immunologie et immunothérapie des cancers, unité 517 mort cellulaire et cancer, IFR 100 et Université de Bourgogne, 7 boulevard Jeanne-d'Arc, 21079 Dijon.
Arnould
Laurent
L
Chantôme
Aurélie
A
Reisser
Daniele
D
Bettaieb
Ali
A
Reveneau
Sylvie
S
Jeannin
Jean-François
JF
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000209:etiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III