Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival
Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival
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DOI：
10.1016/j.cell.2015.08.031
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发表时间：
2015-09-10
期刊：
影响因子：
64.5
通讯作者：
Hoogenraad, Nicholas J.
中科院分区：
文献类型：
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作者：
Johnston, Amelia J.;Murphy, Kate T.;Hoogenraad, Nicholas J.
细胞因子TWEAK及其同源受体Fn 14是TNF/TNFR超家族的成员，在肿瘤中上调。我们发现，Fn 14，当在肿瘤中表达时，引起恶病质，并且针对Fn 14的抗体通过抑制肿瘤诱导的体重减轻而显著延长寿命，尽管对肿瘤生长只有适度的抑制作用。抗Fn 14抗体可预防肿瘤诱导的炎症以及脂肪和肌肉质量的损失。肿瘤中的Fn 14信号而不是宿主中的Fn 14信号负责诱导这种恶病质，因为Fn 14和TWEAK缺陷宿主中的肿瘤发展出与野生型小鼠相当的恶病质。这些结果将Fn 14在伤口修复和肌肉发育中的作用扩展到参与恶病质的病因学，并表明Fn 14抗体可能是治疗恶病质的有希望的方法，从而延长癌症患者的寿命并改善其生活质量。
The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumorinduced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- andTWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients.