Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3.
Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3.
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肿瘤相关中性粒细胞和巨噬细胞相互作用通过激活 STAT3 促进肝内胆管癌进展
DOI：
10.1136/jitc-2020-001946
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发表时间：
2021-03
影响因子：
10.9
通讯作者：
Zhou S
中科院分区：
文献类型：
--
作者：
Zhou Z;Wang P;Sun R;Li J;Hu Z;Xin H;Luo C;Zhou J;Fan J;Zhou S
肿瘤相关中性粒细胞（TANs）和巨噬细胞（TAMs）可各自影响肿瘤生长和转移，但它们在肝内胆管癌（ICC）中的联合作用尚不清楚。方法采用多重免疫荧光染色法检测TANs和TAMs在人源性ICC中的分布，并检测TANs和TAMs单独及联合作用对ICC的影响。然后，我们使用PCR阵列，蛋白质印迹分析和ELISA实验的影响的机制基础进行了研究。最后，我们在由359例ICC患者的原发性肿瘤组织组成的组织微阵列中验证了我们的结果。结果患者ICC标本中TANs和TAMs的空间分布具有相关性。TAN和TAM之间的相互作用增强了体外ICC细胞的增殖和侵袭能力以及ICC小鼠异种移植模型中的肿瘤进展。TAN和TAM分别在共培养中比在单培养中产生更高水平的制瘤素M和白细胞介素-11。这两种细胞因子都激活了ICC细胞中的STAT 3信号。STAT 3的敲低消除了TAN和TAM对ICC的促肿瘤作用。在ICC患者的肿瘤样本中，TAN和TAM水平的升高与p-STAT 3表达的升高相关。所有这三个因素都是患者预后的独立预测因素。结论TANs和TAMs通过激活STAT 3相互作用促进ICC进展。
Background Tumor-associated neutrophils (TANs) and macrophages (TAMs) can each influence cancer growth and metastasis, but their combined effects in intrahepatic cholangiocarcinoma (ICC) remain unclear. Methods We explored the distributions of TANs and TAMs in patient-derived ICC samples by multiplex immunofluorescent staining and tested their separate and combined effects on ICC in vitro and in vivo. We then investigated the mechanistic basis of the effects using PCR array, western blot analysis and ELISA experiments. Finally, we validated our results in a tissue microarray composed of primary tumor tissues from 359 patients with ICC. Results The spatial distributions of TANs and TAMs were correlated with each other in patient-derived ICC samples. Interaction between TANs and TAMs enhanced the proliferation and invasion abilities of ICC cells in vitro and tumor progression in a mouse xenograft model of ICC. TANs and TAMs produced higher levels of oncostatin M and interleukin-11, respectively, in co-culture than in monoculture. Both of those cytokines activated STAT3 signaling in ICC cells. Knockdown of STAT3 abolished the protumor effect of TANs and TAMs on ICC. In tumor samples from patients with ICC, increased TAN and TAM levels were correlated with elevated p-STAT3 expression. All three of those factors were independent predictors of patient outcomes. Conclusions TANs and TAMs interact to promote ICC progression by activating STAT3.
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影响因子：
82.9
作者：
通讯作者：
--
间充质样癌细胞和巨噬细胞之间的正反馈回路对于乳腺癌转移至关重要。
影响因子：
50.3
作者：
Su, Shicheng;Liu, Qiang;Song, Erwei
通讯作者：
Song, Erwei
影响因子：
2.8
作者：
Galdiero, Maria Rosaria;Bonavita, Eduardo;Jaillon, Sebastien
通讯作者：
Jaillon, Sebastien
影响因子：
4.6
作者：
Kim J;Bae JS
通讯作者：
Bae JS
DOI：
10.1038/nrc2734
发表时间：
2009-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Yu H;Pardoll D;Jove R
通讯作者：
Jove R