Tumor-driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL-8.
Tumor-driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL-8.
复制标题
胰腺导管腺癌条件培养基诱导的肿瘤驱动类巨噬细胞通过分泌IL-8促进肿瘤转移
DOI：
10.1002/cam4.1824
复制
发表时间：
2018-11
期刊：
影响因子：
4
通讯作者：
Huang KH
中科院分区：
文献类型：
--
作者：
Chen SJ;Lian GD;Li JJ;Zhang QB;Zeng LJ;Yang KG;Huang CM;Li YQ;Chen YT;Huang KH
肿瘤相关巨噬细胞（Tumor - associated macrophages, tam）是一类丰富的炎症细胞，在肿瘤微环境重塑和肿瘤进展中发挥重要作用。此前，我们发现胰腺导管腺癌（pancreatic ductal adencarcinoma， PDAC）中tam的高密度与淋巴结转移和预后不良相关。因此，本研究旨在探讨tam与PDAC相互作用的机制。THP‐1单核细胞暴露于PDAC细胞产生的条件培养基（CM）中；然后观察单核细胞募集和巨噬细胞分化情况。来自PDAC的CM吸引和极化THP - 1单核细胞到肿瘤驱动的巨噬细胞。mRNA表达、细胞因子分析和ELISA检测表明，IL - 8分泌在肿瘤驱动的类巨噬细胞中增加，并与STAT3通路有关。外源性重组人IL - 8通过上调Twist的表达促进PDAC细胞在体外的运动和体内的转移，Twist介导了癌细胞的上皮-间质转化。此外，通过免疫组织化学分析，IL - 8在肿瘤基质中的表达水平与淋巴结转移、肿瘤CD68阳性巨噬细胞数量和患者预后有关，而与CD163阳性巨噬细胞数量无关。综上所述，这些发现揭示了肿瘤微环境中癌细胞与tam之间的重要相互作用，并提示IL - 8信号可能是PDAC的潜在治疗靶点。
Tumor‐associated macrophages (TAMs) are abundant population of inflammatory cells which play an essential role in remodeling tumor microenvironment and tumor progression. Previously, we found the high density of TAMs was correlated with lymph node metastasis and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Therefore, this study was designed to investigate the mechanisms of interaction between TAMs and PDAC. THP‐1 monocytes were the exposure to conditioned media (CM) produced by PDAC cells; then, monocyte recruitment and macrophage differentiation were assessed. CM from PDAC attracted and polarized THP‐1 monocytes to tumor‐driven like macrophages. mRNA expression cytokine profiling and ELISA identified the IL‐8 secretion was increasing in tumor‐driven like macrophages, and STAT3 pathway was involved. Addition of exogenous recombinant human IL‐8 promoted PDAC cells motility in vitro and metastasis in vivo via upregulating Twist expression, which mediated epithelial‐mesenchymal transition in cancer cells. What is more, IL‐8 expression level in tumor stroma by immunohistochemical analysis was related to lymph node metastasis, the number of tumor CD68 but not CD163 positive macrophages and patient outcome. Taken together, these findings shed light on the important interplay between cancer cells and TAMs in tumor microenvironment and suggested that IL‐8 signaling might be a potential therapeutic target for PDAC.
登录
查看更多内容
影响因子：
4.4
作者：
Lee, Maggie M. K.;Chui, Ricky K. S.;Wong, Yung H.
通讯作者：
Wong, Yung H.
影响因子：
4.6
作者：
Meng, Fanbin;Li, Changling;Song, Shaowei
通讯作者：
Song, Shaowei
影响因子：
6.4
作者：
Helm, Ole;Held-Feindt, Janka;Sebens, Susanne
通讯作者：
Sebens, Susanne
影响因子：
6
作者：
Satoh, Kennichi;Hamada, Shin;Shimosegawa, Tooru
通讯作者：
Shimosegawa, Tooru
影响因子：
6.4
作者：
Ohuchida, Kenoki;Mizumoto, Kazuhiro;Tanaka, Masao
通讯作者：
Tanaka, Masao