Tumour-derived exosomal miR-3473b promotes lung tumour cell intrapulmonary colonization by activating the nuclear factor-κB of local fibroblasts

肿瘤来源的外泌体 miR-3473b 通过激活局部成纤维细胞的核因子-κB 促进肺肿瘤细胞肺内定植

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作者:Cancan Du, Xixi Duan, Xiaohan Yao, Jiajia Wan, Yanru Cheng, Yuan Wang, Yan Yan, Lijing Zhang, Linyu Zhu, Chen Ni, Ming Wang, Zhihai Qin

Abstract

Tumour-derived exosomes have been shown to induce pre-metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC-derived exosomes were mainly engulfed by lung fibroblasts and led to the NF-κB signalling activation. Further studies indicated that the exosomal miR-3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR-3473b could reverse the exosome-mediated NF-κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR-3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.

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