Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition.
Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition.
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肿瘤相关巨噬细胞通过诱导上皮间质转化促进胰腺导管腺癌进展
DOI：
10.18632/aging.202264
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发表时间：
2021-01-10
期刊：
影响因子：
--
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Xiong C;Zhu Y;Xue M;Jiang Y;Zhong Y;Jiang L;Shi M;Chen H
在这项研究中，我们研究了肿瘤相关巨噬细胞（TAMs）在胰腺导管腺癌（PDAC）进展中的作用。CD 68 + TAM水平较高的PDAC患者的总生存期较短。在Transwell试验中，与TAM或TAM细胞的条件培养基（TAM-CM）孵育的PDAC细胞显示出比对照更高的迁移和侵袭率。原位PDAC模型小鼠的PET/CT扫描分析显示，TAM-CM治疗组中的原发性肿瘤生长和肝转移比对照组更大。肝组织的H&E染色显示在TAM-CM治疗组中显著更高数量的转移性结节。TAM-CM的热失活显著降低PDAC细胞的Transwell迁移，表明一种或多种分泌蛋白参与PDAC进展。TAM-CM处理的PDAC细胞的转录组测序分析显示转化生长因子-β（TGF-β）信号通路基因显著富集。Western blot和qRT-PCR分析显示TAM-CM通过TGF-β-Smad 2/3/4-Snail信号轴诱导上皮细胞向间充质细胞转化，增强PDAC细胞迁移。TAMs或TAM-CM的促肿瘤作用可被TGF-β信号通路抑制剂和中和TGF-β抗体所消除。这些结果表明TAM通过TGF-β信号传导途径促进PDAC进展。
In this study, we investigated the role of tumor-associated macrophages (TAMs) in the progression of pancreatic ductal adenocarcinoma (PDAC). PDAC patients with higher levels of CD68+ TAMs exhibited shorter overall survival. In Transwell assays, PDAC cells incubated with TAMs or conditioned media from TAM cells (TAM-CM) showed higher migration and invasion rates than controls. PET/CT scan analysis of orthotopic PDAC model mice revealed greater primary tumor growth and liver metastasis in the TAM-CM treatment group than the controls. H&E staining of liver tissues showed significantly higher numbers of metastatic nodules in the TAM-CM treatment group. Heat inactivation of TAM-CM significantly reduced Transwell migration by PDAC cells, suggesting the involvement of one or more secreted proteins in PDAC progression. Transcriptome sequencing analysis of PDAC cells treated with TAM-CM revealed significant enrichment of transforming growth factor-β (TGF-β) signaling pathway genes. Western blot and qRT-PCR analysis showed that TAM-CM enhanced PDAC migration cells by inducing epithelial-to-mesenchymal transition through the TGF-β-Smad2/3/4-Snail signaling axis. The pro-tumorigenic effects of TAMs or TAM-CM were abolished by TGF-β signaling pathway inhibitors and neutralizing TGF-β antibody. These results demonstrate that TAMs promote PDAC progression through the TGF-β signaling pathway.
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影响因子：
5.7
作者：
Ma, Ying-Yu;He, Xu-Jun;Tao, Hou-Quan
通讯作者：
Tao, Hou-Quan
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
2.6
作者：
Hanada, T;Nakagawa, M;Nomura, Y
通讯作者：
Nomura, Y
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.1
作者：
Fabregat, Isabel;Fernando, Joan;Sancho, Patricia
通讯作者：
Sancho, Patricia