Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization.
Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization.
复制标题
食管癌来源的细胞外囊泡 miR-21-5p 通过破坏巨噬细胞极化促进食管鳞癌细胞的 EMT
DOI：
10.3390/cancers13164122
复制
发表时间：
2021-08-16
期刊：
影响因子：
5.2
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Song J;Yang P;Li X;Zhu X;Liu M;Duan X;Liu R
巨噬细胞极化相关的细胞外囊泡（EV）在肿瘤进展中起着至关重要的作用。miR-21- 5 p在食管鳞状细胞癌（ESCC）发展过程中EV中的作用必须澄清。本研究旨在确定EVs-miR-21- 5 p递送过程中不同极化状态下ESCC细胞和巨噬细胞之间的关系。我们发现M0巨噬细胞摄取了由EC 109或EC 9706细胞分泌的过表达的EVs-miR-21- 5 p，这通过PTEN/AKT/STAT 6途径将它们转化为M2巨噬细胞。这反过来又有助于M2巨噬细胞分泌高水平的TGF-β1，并通过TGF-β/Smad 2轴促进食管癌细胞上皮-间质转化。这些发现表明EVs-miR-21- 5 p可能是ESCC的关键分子。摘要肿瘤相关巨噬细胞（TAMs）的无序极化对肿瘤的进展有重要影响。癌细胞分泌的细胞外囊泡（EV）中的微小RNA（miRNA）可能有助于这一过程。然而，TAMs和EVs-miRNAs介导的调控在食管鳞状细胞癌（ESCC）中的关系仍不清楚。本研究采用免疫亲和磁珠结合抗上皮细胞粘附分子（EpCAM）从食管鳞癌患者血浆中分离并鉴定EVs-miR-21- 5 p。设计体外共培养系统以评估miR-21- 5 p过表达的食管癌细胞对巨噬细胞极化的影响。我们发现佛波醇肉豆蔻酸酯乙酸酯诱导的THP-1巨噬细胞从EC 109或EC 9706细胞摄取EVs-miR-21- 5 p并转化为M2巨噬细胞。这反过来又导致了食管癌细胞的过度迁移和侵袭。这些变化的潜在机制可能涉及通过PTEN/AKT/STAT 6途径上调ESCC衍生的EVs-miR-21- 5 p激活M2巨噬细胞。这可能通过TGF-β/Smad 2信号传导导致食管癌细胞上皮间质转化（EMT）。我们的研究结果表明，通过miR-21- 5 p在肿瘤衍生的EV中的穿梭，肿瘤微环境中M2巨噬细胞极化和食管癌细胞的EMT之间存在正反馈。
Simple Summary Macrophage polarization-associated extracellular vesicles (EVs) play crucial roles in tumor progression. The role of miR-21-5p in EVs during esophageal squamous cell carcinoma (ESCC) development must be clarified. This study aimed to identify the relationship between ESCC cells and macrophages in different polarization states during the delivery of EVs-miR-21-5p. We found that M0 macrophages took up overexpressed EVs-miR-21-5p secreted by EC109 or EC9706 cells, which transformed them into M2 macrophages through the PTEN/AKT/STAT6 pathway. This, in turn, contributed to secretion of high levels of TGF-β1 by M2 macrophages and promoted esophageal cancer cell epithelial-mesenchymal transition via the TGF-β/Smad2 axis. These findings indicate that EVs-miR-21-5p may be a critical molecule for ESCC. Abstract The disorganized polarization of tumor-associated macrophages (TAMs) exerts a critical effect on tumor progression. MicroRNAs (miRNAs) in extracellular vesicles (EVs) secreted from cancer cells may contribute to this process. However, the relationship between TAMs and EVs-miRNAs-mediated regulation in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, immunoaffinity magnetic beads combined with antiepithelial cell adhesion molecules (EpCAM) were used to isolate and identify EVs-miR-21-5p from the plasma of ESCC patients. An in vitro coculture system was designed to evaluate the effect of esophageal cancer cells with miR-21-5p overexpression on macrophage polarization. We found that phorbol myristate acetate-induced THP-1 macrophages took up EVs-miR-21-5p from EC109 or EC9706 cells and were transformed into M2 macrophages. This, in turn, contributed to the excessive migration and invasion of esophageal cancer cells. The mechanism underlying these changes may involve activation of M2 macrophages by upregulated ESCC-derived EVs-miR-21-5p through the PTEN/AKT/STAT6 pathway. This may result in esophageal cancer cell epithelial-mesenchymal transition (EMT) via TGF-β/Smad2 signaling. Our results indicate positive feedback between M2 macrophage polarization and EMT of esophageal cancer cells in the tumor microenvironment via shuttling of miR-21-5p in tumor-derived EVs.
登录
查看更多内容
影响因子：
16
作者：
Mateescu B;Kowal EJ;van Balkom BW;Bartel S;Bhattacharyya SN;Buzás EI;Buck AH;de Candia P;Chow FW;Das S;Driedonks TA;Fernández-Messina L;Haderk F;Hill AF;Jones JC;Van Keuren-Jensen KR;Lai CP;Lässer C;Liegro ID;Lunavat TR;Lorenowicz MJ;Maas SL;Mäger I;Mittelbrunn M;Momma S;Mukherjee K;Nawaz M;Pegtel DM;Pfaffl MW;Schiffelers RM;Tahara H;Théry C;Tosar JP;Wauben MH;Witwer KW;Nolte-'t Hoen EN
通讯作者：
Nolte-'t Hoen EN
DOI：
10.1016/j.ymthe.2017.11.016
发表时间：
2018-02-07
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Hsu YL;Hung JY;Chang WA;Jian SF;Lin YS;Pan YC;Wu CY;Kuo PL
通讯作者：
Kuo PL
影响因子：
8.8
作者：
Aras S;Zaidi MR
通讯作者：
Zaidi MR
影响因子：
50.3
作者：
Ruffell B;Coussens LM
通讯作者：
Coussens LM
DOI：
10.1083/jcb.201212113
发表时间：
2013-02-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Harding CV;Heuser JE;Stahl PD
通讯作者：
Stahl PD