Tumor necrosis factor superfamily member 14 (TNFSF14), LIGHT, is a component of the cytokine network that regulates innate and adaptive immune responses, which promote homeostasis of lymphoid organs, liver, and bone. Metastatic tumors often disrupt the tissue microenvironment, thus altering the homeostasis of the invaded organ; however, the underlying mechanisms required further studies. We investigated the role of LIGHT in osteolytic bone disease induced by metastatic non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC bone metastasis show significantly higher levels of LIGHT expressed in monocytes compared with non-bone metastatic tumors and healthy controls. Serum LIGHT levels were also higher in patients with bone metastases than in controls, suggesting a role for LIGHT in stimulating osteoclast precursors. In bone metastatic patients, we also detected increased RNA expression and serum RANKL levels, thus by adding anti-LIGHT or RANK-fragment crystallizable region (RANK-Fc) in PBMC cultures, a significant inhibition of osteoclastogenesis was observed. To model this observation in mice, we used the mouse lung cancer cell line LLC-1. After intratibial implantation, wild-type mice showed an increased number of osteoclasts but reduced numbers of osteoblasts and decreased osteoid formation. In contrast, Tnfsf14-/- mice showed no significant bone loss or other changes in bone homeostasis associated with this model. These data indicate LIGHT is a key control mechanism for regulating bone homeostasis during metastatic invasion. Thus, LIGHT may be a novel therapeutic target in osteolytic bone metastases. © 2019 American Society for Bone and Mineral Research.

中文翻译：

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LIGHT/TNFSF14 促进非小细胞肺癌患者的溶骨性骨转移。

肿瘤坏死因子超家族成员 14 (TNFSF14)，LIGHT，是调节先天性和适应性免疫反应的细胞因子网络的一个组成部分，可促进淋巴器官、肝脏和骨骼的稳态。转移性肿瘤通常会破坏组织微环境，从而改变受侵器官的稳态；然而，潜在的机制需要进一步研究。我们研究了 LIGHT 在转移性非小细胞肺癌 (NSCLC) 诱导的溶骨性骨病中的作用。与非骨转移肿瘤和健康对照相比，诊断为 NSCLC 骨转移的患者在单核细胞中表达的 LIGHT 水平显着升高。骨转移患者的血清 LIGHT 水平也高于对照组，这表明 LIGHT 在刺激破骨细胞前体中的作用。在骨转移患者中，我们还检测到 RNA 表达和血清 RANKL 水平增加，因此通过在 PBMC 培养物中添加抗 LIGHT 或 RANK 片段结晶区 (RANK-Fc)，观察到破骨细胞生成的显着抑制。为了在小鼠中模拟这种观察，我们使用了小鼠肺癌细胞系 LLC-1。胫骨内植入后，野生型小鼠的破骨细胞数量增加，但成骨细胞数量减少，类骨质形成减少。相比之下，Tnfsf14-/- 小鼠没有显示出与该模型相关的显着骨丢失或其他骨稳态变化。这些数据表明 LIGHT 是在转移性侵袭过程中调节骨稳态的关键控制机制。因此，LIGHT 可能是溶骨性骨转移的新治疗靶点。© 2019 美国骨与矿物研究学会。