Macrophage Migratory Inhibitory Factor (MIF) promotes bladder cancer progression via increasing proliferation and angiogenesis
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en augmentant la prolifération cellulaire et l'angiogenèse, le facteur inhibiteur de la migration des macrophages, MIF, favorise le développement d'un cancer de la vessie
Macrophage migratory inhibitory factor (MIF) is a proinflammatory cytokine shown to promote tumorigenesis. Using the N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) model of bladder cancer, we previously showed that MIF knockout mice display decreased angiogenesis and invasion compared to wild-type. This study examines the role of MIF in bladder cancer via use of oral inhibitors of MIF. In vitro, high grade bladder cancer cells were treated with rhMIF+/- inhibitor. Measurements included cell counts, proliferation by 3H-thymidine incorporation (TdR), ERK phosphorylation by Western analysis, mRNA expression by quantitative PCR and protein secretion by ELISA. Treatment with rhMIF increased ERK phosphorylation, cell counts, TdR and mRNA expression and protein secretion of VEGF, which were blocked by specific inhibitors of ERK and MIF. In vivo, three month-old male C57Bl/6 mice were given BBN for 22 and 16 weeks in study 1 and 2, respectively. Mice (n=8-10/group) were gavaged with vehicle or doses of MIF inhibitors daily from weeks 16-22 in both studies. Average bladder weights, reflecting tumor mass, tumor stage/burden, mitotic rate and proliferation indices, and micro-vessel densities (MVD) were reduced in inhibitor groups vs controls. In summary, MIF promotes bladder cancer via increasing cell proliferation and angiogenesis and oral inhibitors of MIF may prove useful in treatment of this disease.
http://carcin.oxfordjournals.org/content/early/2013/07/03/carcin.bgt239.abstract