Department of Thoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Department of Thoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu, China; Department of Thoracic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Cancer Lett. 2022 Feb 1;526:205-216. doi: 10.1016/j.canlet.2021.10.045. Epub 2021 Nov 25.
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.
肿瘤相关巨噬细胞（TAMs）是肿瘤微环境的主要组成部分，有助于肺腺癌（LUAD）的转移。最近有报道称，TAM 衍生的外泌体在肿瘤发生和进展中的生物标志物发现方面具有潜力。然而，关于 LUAD 中巨噬细胞衍生的外泌体的研究仍然有限。我们在体内和体外研究了 M2 巨噬细胞衍生的外泌体在 LUAD 中的作用及其潜在机制。结果表明，M2 巨噬细胞的浸润与 LUAD 的转移呈正相关。M2 巨噬细胞衍生的外泌体可以被 LUAD 细胞摄取，从而促进细胞迁移、侵袭和血管生成。此外，miR-942 可以被 M2 巨噬细胞分泌的外泌体包裹。从机制上讲，外泌体 miR-942 通过结合 FOXO1 的 3'-UTR 区域来调节 FOXO1 蛋白表达，从而进一步减轻 LUAD 细胞中β-catenin 的抑制。综上所述，我们证明了 M2 巨噬细胞衍生的含有 miRNA 的外泌体促进 LUAD 细胞的侵袭和迁移，并促进血管生成，从而为转移性 LUAD 提供了新的治疗靶点。
