Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination.
Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination.
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M2表型的肿瘤相关巨噬细胞有助于胃癌腹膜转移的进展。
DOI：
10.1007/s10120-015-0579-8
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发表时间：
2016-10
期刊：
影响因子：
7.4
通讯作者：
Ohta, Tetsuo
中科院分区：
文献类型：
--
作者：
Yamaguchi, Takahisa;Fushida, Sachio;Yamamoto, Yasuhiko;Tsukada, Tomoya;Kinoshita, Jun;Oyama, Katsunobu;Miyashita, Tomoharu;Tajima, Hidehiro;Ninomiya, Itasu;Munesue, Seiichi;Harashima, Ai;Harada, Shinichi;Yamamoto, Hiroshi;Ohta, Tetsuo
已知M2表型的肿瘤相关巨噬细胞（TAM）促进肿瘤增殖并且与许多癌症的不良预后相关。在这里，我们研究了M2巨噬细胞是否参与胃癌腹膜播散的发展。应用流式细胞术和实时荧光定量聚合酶链反应（PCR）技术，对胃癌患者腹腔巨噬细胞的特性进行了研究。采用体外直接或间接共培养系统和小鼠体内异种移植模型，观察M2巨噬细胞对胃癌细胞系MKN 45表型变化的影响。胃癌伴腹膜转移患者腹腔巨噬细胞M2表型（CD 68 + CD 163+或CD 68 + CD 204+）的数量显著高于无腹膜转移者。在TAM中还证实了M2相关信使RNA（IL-10、血管内皮生长因子A、血管内皮生长因子C、基质金属蛋白酶1和双调蛋白）的高表达和M1相关信使RNA（TNF-α、CD 80、CD 86和IL-12 p40）的低表达。巨噬细胞与胃癌细胞共培养可使M1表型转化为M2表型。此外，MKN 45细胞与M2巨噬细胞的共存导致癌细胞增殖和异种移植模型中肿瘤生长的加速。腹膜内转移的胃癌患者腹膜内TAM向M2表型极化，可能有助于肿瘤的增殖和进展。因此，腹腔内TAMs有望成为治疗胃癌腹膜播散的一个有前途的靶点。
Tumor-associated macrophages (TAMs) of the M2 phenotype are known to promote tumor proliferation and to be associated with a poor prognosis in numerous cancers. Here, we investigated whether M2 macrophages participate in the development of peritoneal dissemination in gastric cancer. The characteristics of peritoneal macrophages in gastric cancer patients with or without peritoneal dissemination were examined by flow cytometry and the real-time quantitative polymerase chain reaction. The effects of M2 macrophages on phenotypic changes of the gastric cancer cell line MKN45 were assessed with a direct or indirect co-culture system in vitro and an in vivo mouse xenograft model. The number of peritoneal macrophages with the M2 phenotype (CD68+CD163+ or CD68+CD204+) was significantly higher in gastric cancer patients with peritoneal dissemination than in those without peritoneal dissemination. Higher expression of the M2-related messenger RNAs (IL-10, vascular endothelial growth factor A, vascular endothelial growth factor C, matrix metalloproteinase 1, and amphiregulin) and lower expression of M1-related messenger RNAs (TNF-α, CD80, CD86, and IL-12p40) were also confirmed in the TAMs. Macrophage co-culture with gastric cancer cells converted M1 phenotype into M2 phenotype. Moreover, the coexistence of MKN45 cells with M2 macrophages resulted in cancer cell proliferation and an acceleration of tumor growth in the xenograft model. Intraperitoneal TAMs in gastric cancer patients with peritoneal dissemination were polarized to the M2 phenotype, and could contribute to tumor proliferation and progression. Therefore, intraperitoneal TAMs are expected to be a promising target in the treatment of peritoneal dissemination in gastric cancer.
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影响因子：
3.7
作者：
Galizia, Gennaro;Lieto, Eva;Ciardiello, Fortunato
通讯作者：
Ciardiello, Fortunato
影响因子：
4.3
作者：
Jaguin, Marie;Houlbert, Noemie;Lecureur, Valerie
通讯作者：
Lecureur, Valerie
影响因子：
64.5
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Qian BZ;Pollard JW
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Pollard JW
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6.4
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Reinartz, Silke;Schumann, Tim;Finkernagel, Florian;Wortmann, Annika;Jansen, Julia M.;Meissner, Wolfgang;Krause, Michael;Schwoerer, Anne-Marie;Wagner, Uwe;Mueller-Bruesselbach, Sabine;Mueller, Rolf
通讯作者：
Mueller, Rolf
影响因子：
4.8
作者：
Brown, CL;Meise, KS;Dempsey, PJ
通讯作者：
Dempsey, PJ