Nature：紫外线诱导黑素瘤发生的机制
生物谷
暴露于紫外线辐射已被发现与黑素瘤形成有关。现在，Glenn Merlino及其同事在一个小鼠模型中发现，UVB辐照能帮助吸引巨噬细胞，后者能产生干扰素-γ，来促进黑素瘤的形成。这项研究表明，以干扰素-γ为目标的药物也许对黑素瘤患者有治疗潜力。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09666
Interferon-γ links ultraviolet radiation to melanomagenesis in mice
M. Raza Zaidi,Sean Davis,Frances P. Noonan,Cari Graff-Cherry,Teresa S. Hawley,Robert L. Walker,Lionel Feigenbaum,Elaine Fuchs,Lyudmila Lyakh,Howard A. Young,Thomas J. Hornyak,Heinz Arnheiter,Giorgio Trinchieri,Paul S. Meltzer,Edward C. De Fabo& Glenn Merl
Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological 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 transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA3, 4. However, the 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, identifying a novel candidate therapeutic target for a subset of melanoma patients.
