Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University , Zunyi, China.
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China.
Cell Cycle. 2021 Feb;20(4):434-444. doi: 10.1080/15384101.2021.1878326. Epub 2021 Jan 31.
Tumor-associated macrophages contribute to cell growth, development, and metastasis in various cancers. However, the underlying mechanisms of M2 macrophage that modulate the progression of gastric cancer (GC) remain largely unknown. In this study, we detected the ratio of macrophages in GC tissues and found that the proportion of M2 macrophages was increased in GC tissues. We then co-cultured GC cells with M1 and M2 macrophages, respectively, and then assessed cell proliferation and tumorigenicity of GC cells by MTT and colony formation assay. The results indicated that M2 macrophages promoted the proliferation of GC cells, but M1 not. Besides, GW4869, an exosomes inhibitor, reduced the effects induced by M2 macrophage. Then, we isolated and identified exosomes derived from M1 and M2 macrophage, and confirmed that the exosomes could be taken up by GC cells. We demonstrated that M2 macrophage-exosomes could induce the proliferation and tumorigenesis and . Moreover, miR-487a was enriched in M2 macrophage-exosomes and further determined that miR-487a exert the functions by targeting TIA1. In conclusion, exosomal miR-487a derived from M2 macrophage promotes the proliferation and tumorigenesis in gastric cancer, and the novel findings might be helpful to the development of novel diagnostic and therapeutic methods in GC.
肿瘤相关巨噬细胞有助于各种癌症中的细胞生长、发育和转移。然而，M2 巨噬细胞调节胃癌（GC）进展的潜在机制在很大程度上仍不清楚。在本研究中，我们检测了 GC 组织中的巨噬细胞比例，发现 GC 组织中 M2 巨噬细胞的比例增加。然后，我们分别将 GC 细胞与 M1 和 M2 巨噬细胞共培养，然后通过 MTT 和集落形成实验评估 GC 细胞的增殖和致瘤性。结果表明，M2 巨噬细胞促进 GC 细胞的增殖，但 M1 则不然。此外，外泌体抑制剂 GW4869 降低了 M2 巨噬细胞诱导的作用。然后，我们分离并鉴定了源自 M1 和 M2 巨噬细胞的外泌体，并证实外泌体可以被 GC 细胞摄取。我们证明了 M2 巨噬细胞衍生的外泌体可以诱导 GC 细胞的增殖和致瘤性。此外，miR-487a 在 M2 巨噬细胞衍生的外泌体中富集，并进一步确定 miR-487a 通过靶向 TIA1 发挥作用。总之，M2 巨噬细胞衍生的外泌体 miR-487a 促进了胃癌的增殖和致瘤性，这些新发现可能有助于开发 GC 的新的诊断和治疗方法。
