Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Minimally Invasive Therapy Center, Okayama University Hospital, Okayama, Japan.
BMC Cancer. 2021 Jan 28;21(1):102. doi: 10.1186/s12885-021-07816-6.
Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated.
The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored.
Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein.
EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment.
胃癌常常发生腹膜扩散。在有腹膜扩散的胃癌患者的腹腔中存在肿瘤相关巨噬细胞（TAMs），促进肿瘤进展。然而，巨噬细胞在腹腔中分化为肿瘤相关巨噬细胞的机制尚不清楚。在这项研究中，研究了胃癌衍生的细胞外囊泡（EVs）与巨噬细胞之间的相互作用。
研究了胃癌患者腹腔渗出液中巨噬细胞与 EVs 的关联，或从胃癌细胞系中观察到的关联，并进一步探讨了它们在巨噬细胞分化和增强胃癌恶性程度中的作用。
腹腔渗出液的免疫荧光检测显示，M2 巨噬细胞与癌细胞一起在腹腔中占优势。从胃癌细胞中纯化的 EVs 以及恶性腹水将外周血单核细胞来源的巨噬细胞分化为 M2 样表型，这通过其形态和 CD163/206 的表达得到证实。由胃癌衍生的 EVs 分化的巨噬细胞促进了胃癌细胞的迁移能力，并且 EVs 携带 STAT3 蛋白。
胃癌衍生的 EVs 通过影响巨噬细胞表型发挥作用，这表明这可能是形成腹腔内癌症微环境的潜在机制的一部分。
