Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils
Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils
复制标题
肿瘤外泌体 RNA 通过激活肺泡上皮 TLR3 招募中性粒细胞来促进肺转移前生态位形成。
DOI：
10.1016/j.ccell.2016.06.021
复制
发表时间：
2016-08-08
期刊：
影响因子：
50.3
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Liu, Yanfang;Gu, Yan;Cao, Xuetao
由原发性肿瘤衍生元件训练的转移前小生境有助于癌症转移。然而，宿主间质细胞在转移性小生境形成和器官特异性转移向性中的作用尚不清楚。在这里，我们证明了肺上皮细胞通过Toll样受体3（TLR3）感知肿瘤外泌体RNA，对启动中性粒细胞募集和肺转移性小生境形成至关重要。TLR3缺陷型小鼠在自发转移模型中显示肺转移减少。机制上，富含小核RNA的原发性肿瘤来源的外泌体RNA激活肺上皮细胞中的TLR 3，从而诱导肺中的趋化因子分泌并促进嗜中性粒细胞募集。肿瘤外泌体RNA和宿主肺上皮细胞TLR3活化的转移轴的鉴定提供了控制癌症向肺转移的潜在靶点。
The pre-metastatic niche educated by primary tumor-derived elements contributes to cancer metastasis. However, the role of host stromal cells in metastatic niche formation and organ-specific metastatic tropism is not clearly defined. Here, we demonstrate that lung epithelial cells are critical for initiating neutrophil recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs via Toll-like receptor 3 (TLR3). TLR3-deficient mice show reduced lung metastasis in the spontaneous metastatic models. Mechanistically, primary tumor-derived exosomal RNAs, which are enriched in small nuclear RNAs, activate TLR3 in lung epithelial cells, consequently inducing chemokine secretion in the lung and promoting neutrophil recruitment. Identification of metastatic axis of tumor exosomal RNAs and host lung epithelial cell TLR3 activation provides potential targets to control cancer metastasis to the lung.