M1-like tumor-associated macrophages activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma.
M1-like tumor-associated macrophages activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma.
复制标题
外泌体转移的 THBS1 激活的 M1 样肿瘤相关巨噬细胞促进口腔鳞状细胞癌的恶性迁移
DOI：
10.1186/s13046-018-0815-2
复制
发表时间：
2018-07-09
期刊：
影响因子：
--
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Xiao M;Zhang J;Chen W;Chen W
背景针对肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）的治疗策略已被提出。巨噬细胞在人类上皮癌肿瘤发生过程中微环境中的功能改变仍然知之甚少。本研究旨在探讨口腔鳞状细胞癌（OSCC）发生发展过程中巨噬细胞表型的变化。我们使用流式细胞术、Luminex测定和定量实时PCR测定来测量巨噬细胞的表型改变。细胞内信号通路分析，质谱蛋白质组学，蛋白质印迹，酶联免疫吸附试验，免疫组织化学染色，和生物信息学分析进行揭示潜在的mechanism.ResultsTHP-1衍生和PBMC衍生的巨噬细胞表现出M1样表型，但不M2样表型，当处理与CM从口腔鳞癌细胞，但不与CM从正常上皮或白斑细胞。进一步的研究表明，巨噬细胞在早期阶段通过p38、Akt和SAPK/JNK信号转导摄取从OSCC细胞释放的外泌体而被激活。我们进一步提供证据表明，THBS 1来源于OSCC外泌体参与了巨噬细胞向M1样表型的极化。反过来，CM从外泌体诱导M1样TAMs和显着促进迁移OSCC cells.ConclusionsWe提出了一种新的旁分泌环癌细胞和巨噬细胞之间的基础上外泌体从OSCC。因此，通过外泌体极化的M1样TAM的靶向管理显示出作为控制OSCC中癌迁移的治疗靶点的巨大潜力。
BackgroundTreatment strategies targeting tumor-associated macrophages (TAMs) have been proposed in cancer areas. The functional alterations of macrophages in the microenvironment during the tumorigenesis of human epithelial cancer remain poorly understood. Here, we explored phenotypic alteration of macrophages during the development of oral squamous cell carcinoma (OSCC).MethodsConditioned media (CM) and exosome supernatants were harvested from normal oral epithelium, oral leukoplakia cells and OSCC cells. We measured phenotypic alteration of macrophages using flow cytometry, luminex assays, and quantitative real-time PCR assay. Intracellular signaling pathway analysis, mass spectrometry proteomics, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and bioinformatics analysis were performed to uncover the underlying mechanisms.ResultsTHP-1-derived and PBMCs derived macrophages exhibited an M1-like phenotype but not M2-like phenotype, when treated with CM from OSCC cells but not with the CM from normal epithelium or leukoplakia cells. Further investigations revealed that macrophages were activated by taking up exosomes released from OSCC cells through p38, Akt, and SAPK/JNK signaling at the early phase. We further provided evidences that THBS1 derived from OSCC exosomes participated in the polarization of macrophages to an M1-like phenotype. Reciprocally, CM from exosomes induced M1-like TAMs and significantly promoted migration of OSCC cells.ConclusionsWe proposed a novel paracrine loop between cancer cells and macrophages based on exosomes from OSCC. Therefore, target management of M1-like TAMs polarized by exosomes shows great potential as a therapeutic target for the control of cancerous migration in OSCC.
登录
查看更多内容
影响因子：
--
作者：
Estko M;Baumgartner S;Urech K;Kunz M;Regueiro U;Heusser P;Weissenstein U
通讯作者：
Weissenstein U
影响因子：
37.8
作者：
de Couto G;Gallet R;Cambier L;Jaghatspanyan E;Makkar N;Dawkins JF;Berman BP;Marbán E
通讯作者：
Marbán E
影响因子：
4.7
作者：
He, Mian;Qin, Hao;Wong, Nathalie
通讯作者：
Wong, Nathalie
影响因子：
20.1
作者：
Liu Z;Morgan S;Ren J;Wang Q;Annis DS;Mosher DF;Zhang J;Sorenson CM;Sheibani N;Liu B
通讯作者：
Liu B
影响因子：
7.2
作者：
Berchem G;Noman MZ;Bosseler M;Paggetti J;Baconnais S;Le Cam E;Nanbakhsh A;Moussay E;Mami-Chouaib F;Janji B;Chouaib S
通讯作者：
Chouaib S