Tumor-associated macrophages derived CCL18 promotes metastasis in squamous cell carcinoma of the head and neck.
Tumor-associated macrophages derived CCL18 promotes metastasis in squamous cell carcinoma of the head and neck.
复制标题
肿瘤相关巨噬细胞衍生的 CCL18 促进头颈部鳞状细胞癌的转移
DOI：
10.1186/s12935-018-0620-1
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发表时间：
2018
影响因子：
5.8
通讯作者：
Huang D
中科院分区：
文献类型：
--
作者：
She L;Qin Y;Wang J;Liu C;Zhu G;Li G;Wei M;Chen C;Liu G;Zhang D;Chen X;Wang Y;Qiu Y;Tian Y;Zhang X;Liu Y;Huang D
肿瘤微环境中选择性活化的巨噬细胞被定义为促进癌症进展的M2肿瘤相关巨噬细胞（M2 tam）。然而，M2 tam与头颈部鳞状细胞癌（SCCHN）中癌细胞之间的交流机制在很大程度上仍然未知。采用实时荧光定量PCR、western blotting、酶联免疫吸附法和流式细胞术检测M2 - TAMs、上皮-间质转化（epithelial-mesenchymal transition， EMT）和干性相关基因mRNA和蛋白表达。采用创面愈合试验和Transwell侵袭试验检测其侵袭和迁移。用成球法检测SCCHN细胞的干性。采用rna测序和随后的生物信息学分析来确定转录组的变化。THP-1单核细胞成功极化为m2样tam，表现为CCL18、IL-10和CD206 mRNA和蛋白表达增加。来自m2样tam的条件培养基促进了SCCHN细胞的迁移和侵袭，这伴随着EMT的发生和干性的增强。重要的是，CCL18中和抗体部分消除了条件培养基对m2样tam的影响。此外，重组人CCL18 （rhCCL18）在体外也相应地促进了SCCHN的恶性生物学行为。最后，rna测序分析发现，rhCCL18刺激的基因上调331个，下调363个，在10条癌症相关信号通路中均有统计学富集。这些发现表明，来自m2样tam的CCL18通过诱导体外SCCHN的EMT和癌干性来促进转移。本文的在线版本（10.1186/s12935-018-0620-1）包含补充材料，授权用户可使用。
Alternatively activated macrophages in tumor microenvironment is defined as M2 tumor-associated macrophages (M2 TAMs) that promote cancer progression. However, communicative mechanisms between M2 TAMs and cancer cells in squamous cell carcinoma of head and neck (SCCHN) remain largely unknown. Quantitative real-time PCR, western blotting, enzyme-linked immunosorbent assay and flow cytometry were applied to quantify mRNA and protein expression of genes related to M2 TAMs, epithelial–mesenchymal transition (EMT) and stemness. Wounding-healing and Transwell invasion assays were performed to detect the invasion and migration. Sphere formation assay was used to detect the stemness of SCCHN cells. RNA-sequencing and following bioinformatics analysis were used to determine the alterations of transcriptome. THP-1 monocytes were successfully polarized into M2-like TAMs, which was manifested by increased mRNA and protein expression of CCL18, IL-10 and CD206. Conditioned medium from M2-like TAMs promoted the migration and invasion of SCCHN cells, which was accompanied by the occurrence of EMT and enhanced stemness. Importantly, CCL18 neutralizing antibody partially abrogated these effects that caused by conditional medium from M2-like TAMs. In addition, recombinant human CCL18 (rhCCL18) correspondingly promoted the malignant biological behaviors of SCCHN in vitro. Finally, RNA-sequencing analysis identified 331 up-regulated and 363 down-regulated genes stimulated by rhCCL18, which were statistically enriched in 10 cancer associated signaling pathways. These findings indicate that CCL18 derived from M2-like TAMs promotes metastasis via inducing EMT and cancer stemness in SCCHN in vitro. The online version of this article (10.1186/s12935-018-0620-1) contains supplementary material, which is available to authorized users.
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影响因子：
37.3
作者：
Lane D;Matte I;Laplante C;Garde-Granger P;Carignan A;Bessette P;Rancourt C;Piché A
通讯作者：
Piché A
影响因子：
30.5
作者：
Monticelli LA;Buck MD;Flamar AL;Saenz SA;Tait Wojno ED;Yudanin NA;Osborne LC;Hepworth MR;Tran SV;Rodewald HR;Shah H;Cross JR;Diamond JM;Cantu E;Christie JD;Pearce EL;Artis D
通讯作者：
Artis D
影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
影响因子：
--
作者：
Lin, Zeyu;Li, Wenbin;Ouyang, Nengtai
通讯作者：
Ouyang, Nengtai
影响因子：
20.3
作者：
Biswas, SK;Gangi, L;Sica, A
通讯作者：
Sica, A