M2 macrophage-derived exosomes promote lung adenocarcinoma progression by delivering miR-942

• Published in: Cancer letters 2022-02, Vol.526, p.205-216
• Main Authors: Wei, Ke, Ma, Zijian, Yang, Fengming, Zhao, Xin, Jiang, Wei, Pan, Chunfeng, Li, Zhihua, Pan, Xianglong, He, Zhicheng, Xu, Jing, Wu, Weibing, Xia, Yang, Chen, Liang
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Adenocarcinoma; Adenocarcinoma of Lung - genetics; Angiogenesis; Animals; Antibodies; Blood vessels; Cell adhesion & migration; Cell culture; Communication; Cytokines; Disease Progression; Exosomes; Exosomes - metabolism; FOXO1; FOXO1 protein; Humans; Leukocyte migration; Lung cancer; Lung Neoplasms - genetics; Macrophages; Macrophages - metabolism; Metastases; Metastasis; Mice; Mice, Inbred NOD; MicroRNAs; MicroRNAs - metabolism; Microscopy; miRNA; TAMs; Therapeutic targets; Transfection; Tumor microenvironment; Tumors; β-Catenin
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.10.045

Tumor-associated macrophages (TAMs) are the major components of the tumor microenvironment that contribute to metastasis in lung adenocarcinoma (LUAD). The potential of TAM-derived exosomes for biomarker discovery in tumor initiation and progression has been recently reported. However, studies on macrophage-derived exosomes in LUAD remain limited. We investigated the role of M2 macrophage-derived exosomes in LUAD both in vivo and in vitro and its underlying mechanism. We showed that the infiltration of M2 macrophages was positively correlated with LUAD metastasis. M2 macrophage-derived exosomes could be taken up by LUAD cells to promote cell migration, invasion, and angiogenesis. Furthermore, miR-942 could be packaged into exosomes secreted by M2 macrophages. Mechanistically, exosomal miR-942 regulates FOXO1 protein expression by binding to the 3′-UTR region of FOXO1 and further alleviates β-catenin inhibition in LUAD cells. Collectively, we demonstrated that M2 macrophage-derived miRNA-containing exosomes promote LUAD cell invasion and migration and facilitate angiogenesis, thereby providing a new therapeutic target for metastatic LUAD. •Metastatic lung adenocarcinoma tissues had high M2 macrophage infiltration.•M2 macrophage-derived exosomal miR-942 promoted lung tumor metastasis in vivo.•M2 macrophage-derived exosomal miR-942 induced angiogenesis in vivo.•miR-942 regulates FOXO1 expression to activate the Wnt/β-catenin pathway.