title: Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils.
abstract: 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.
authors: National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Yanfang
authors: Y
authors: Liu
authors: National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Yan
authors: Y
authors: Gu
authors: National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Yanmei
authors: Y
authors: Han
authors: National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Qian
authors: Q
authors: Zhang
authors: National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Zhengping
authors: Z
authors: Jiang
authors: National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Xiang
authors: X
authors: Zhang
authors: National Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors: Bo
authors: B
authors: Huang
authors: National Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors: Xiaoqing
authors: X
authors: Xu
authors: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Jianming
authors: J
authors: Zheng
authors: National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address: caoxt@immunol.org.
authors: Xuetao
authors: X
authors: Cao
mesh_terms: D000818:Animals; D001483:Base Sequence; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D055354:Exosomes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D020556:Neutrophil Infiltration / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D012334:RNA, Neoplasm; D012342:RNA, Small Nuclear; C495344:TLR3 protein, human; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3
keywords: TLR3; alveolar epithelial cell; exosomal RNA; metastasis; pre-metastatic niche