Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, whose incidence continues to rise.,Epidemiological studies reveal that the major etiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood1,2.,We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor (HGF/SF) transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and etiologic criteria, but only when irradiated as neonatal pups with UVB, not UVA3,4.,However, mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown.,Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation.,We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion.,UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons.,IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2.,Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival.,IFN-γ-producing macrophages were also identified in 70% of human melanomas examined.,Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, and suggest that IFN-γ-R signaling represents a novel therapeutic melanoma target.
Statins induces cell cycle arrest, apoptosis, reduction of angiogenic factors, inhibition of the endothelial growth factor, impairing tissue adhesion and attenuation of the resistance mechanisms.,The aim of this study was evaluate the anti-tumoral activity of simvastatin in a B16F10 melanoma-mouse model.,Melanoma cells were treated with different concentrations of simvastatin and assessed by viability methods.,Melanoma cells (5 × 104) were implanted in two month old C57Bl6/J mice.,Around 7 days after cells injection, the oral treatments were started with simvastatin (5 mg/kg/day, p.o.).,Tumor size, hematological and biochemical analyses were evaluated.,Simvastatin at a concentration of 0.8 μM, 1.2 μM and 1.6 μM had toxic effect.,Concentration of 1.6 μM induced a massive death in the first 24 h of incubation.,Simvastatin at 0.8 μM induces early cell cycle arrest in G0/G1, followed by increase of hypodiploidy.,Tumor size were evaluated and the difference of treated group and control, after ten days, demonstrates that simvastatin inhibited the tumor expansion in 68%.,Simvastatin at 1.6 μM, presented cytototoxicity after 72 h of treatment, with an intense death.,In vivo, simvastatin being potentially useful as an antiproliferative drug, with an impairment of growth after ten days.