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源自胃癌外泌体的miR-151-3p诱导巨噬细胞的M2表型极化并促进肿瘤生长

[miR-151-3p derived from gastric cancer exosomes induces M2-phenotype polarization of macrophages and promotes tumor growth].

作者信息

Xie Shilin, Zhu Yuekun, Wang Shuo, Yang Xiuding, Yuan Xiaowei, Piao Daxun

机构信息

Surgery (general surgery), The first clinical medical college affiliated to Harbin Medical University, Harbin 150000, China.

Surgery (general surgery), The first clinical medical college affiliated to Harbin Medical University, Harbin 150000, China. *Corresponding author, E-mail:

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2022 Jul;38(7):584-589.

Abstract

Objective To investigate whether exosomes derived from gastric cancer cells can affect macrophages in tumor microenvironment through miR-151-3p. Methods The expression of miR-151-3p in tumor tissues of patients with gastric cancer and normal tissues was detected by real time quantitative PCR; Gastric cancer cells overexpressing miR-151-3p were constructed, and exosomes were isolated and identified. The expression of CD11b and CD163 markers on RAW264.7 cells co-incubated with exosomes were detected by flow cytometry, and the effects of exosome carrying miR-151-3p on tumor growth and tumor-associated macrophages were evaluated in mice transplanted tumor model. Results The results of real time quantitative PCR showed that the level of miR-151-3p in gastric tumor tissues was significantly higher than that in normal tissues, and the content of miR-151-3p in gastric juice of most patients after operation was lower than that before operation; The content of miR-151-3p in exosomes of tumor cells overexpressing miR-151-3p was also significantly higher than that of untransfected cells. Exosomes carrying miR-151-3p can induce phenotypic differentiation of M2 in co-incubation with RAW264.7 cells. Similarly, tumor transplantation model also showed that exosomes carrying miR-151-3p can induce tumor-associated macrophages to polarize to M2 and promote tumor growth. Conclusion miR-151-3p derived from gastric cancer exosomes can induce the polarization of M2 macrophages and promote the growth of gastric cancer. The treatment of miR-151-3p may destroy the tumor microenvironment of immunosuppression, which assists the anti-tumor immunotherapy.

摘要

目的 探讨胃癌细胞来源的外泌体是否能通过miR-151-3p影响肿瘤微环境中的巨噬细胞。方法 采用实时定量PCR检测胃癌患者肿瘤组织及正常组织中miR-151-3p的表达;构建过表达miR-151-3p的胃癌细胞,分离并鉴定外泌体。采用流式细胞术检测与外泌体共孵育的RAW264.7细胞上CD11b和CD163标志物的表达,并在小鼠移植瘤模型中评估携带miR-151-3p的外泌体对肿瘤生长及肿瘤相关巨噬细胞的影响。结果 实时定量PCR结果显示,胃癌组织中miR-151-3p水平显著高于正常组织,多数患者术后胃液中miR-151-3p含量低于术前;过表达miR-151-3p的肿瘤细胞外泌体中miR-151-3p含量也显著高于未转染细胞。携带miR-151-3p的外泌体与RAW264.7细胞共孵育可诱导M2型表型分化。同样,肿瘤移植模型也显示,携带miR-151-3p的外泌体可诱导肿瘤相关巨噬细胞向M2型极化并促进肿瘤生长。结论 胃癌外泌体来源的miR-151-3p可诱导M2型巨噬细胞极化并促进胃癌生长。对miR-151-3p的治疗可能破坏免疫抑制的肿瘤微环境,辅助抗肿瘤免疫治疗。

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