Daintain/AIF-1 promotes breast cancer cell migration by up-regulated TNF-α via activate p38 MAPK signaling pathway
Daintain/AIF-1 promotes breast cancer cell migration by up-regulated TNF-α via activate p38 MAPK signaling pathway
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DOI：
10.1007/s10549-011-1519-x
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Chen, Zhengwang
中科院分区：
文献类型：
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作者：
Li, Tao;Feng, Zhiguo;Chen, Zhengwang
肿瘤相关巨噬细胞可以释放多种生长因子、蛋白水解酶、细胞因子和炎症介质。其中许多因素是癌症转移的关键因素。Daintain/AIF-1是一种巨噬细胞衍生的炎症细胞因子，它定义了肿瘤相关活化巨噬细胞/小胶质细胞的一个独特亚群。既往研究表明，daintain/AIF-1可通过激活NF-kappa B/cyclin D1通路促进乳腺癌增殖，促进肿瘤生长。然而，Daintain/AIF-1对细胞迁移和肿瘤转移的影响尚未见报道。在此，我们使用模拟肿瘤微环境，将乳腺癌细胞系MDA-MB-231和MCF-7细胞与巨噬细胞条件培养基（含或不含纯化的daintain/AIF-1多肽）孵育，以评估细胞迁移。结果表明，daintain/AIF-1以上调tnf - α的方式促进MDA-MB-231和MCF-7细胞的迁移。进一步研究发现，daintain/AIF-1激活p38 MAPK信号通路，促进MDA-MB-231和MCF-7细胞中tnf - α的上调。因此，这种新的daintain/AIF-1-p38- tnf - α通路和对daintain/AIF-1的了解可能在癌症治疗过程中控制肿瘤转移方面具有潜在的益处。
Tumor-associated macrophages can release a vast diversity of growth factors, proteolytic enzymes, cytokines, and inflammatory mediators. Many of these factors are key agents in cancer metastasis. Daintain/AIF-1 is a macrophage-derived inflammatory cytokine which defined a distinct subset of tumor-associated activated macrophages/microglial cells. Previous study demonstrated that daintain/AIF-1 could promote breast cancer proliferation through activating NF-kappa B/cyclin D1 pathway and facilitate tumor growth. However, the effect of Daintain/AIF-1 on cell migration and cancer metastasis has never been reported. Herein, we used a mimic tumor microenvironment by incubating breast cancer cell lines, MDA-MB-231 and MCF-7 cells, with macrophage-conditioned medium with or without purified daintain/AIF-1 polypeptide to evaluate cell migration. Results indicated that daintain/AIF-1 enhanced the migration of MDA-MB-231 and MCF-7 cells in the manner of TNF-alpha up-regulation. Further study found that daintain/AIF-1 activates p38 MAPK signaling pathway contributing to up-regulation of TNF-alpha in MDA-MB-231 and MCF-7 cells. Therefore, this novel daintain/AIF-1-p38-TNF-alpha pathway and insight into daintain/AIF-1 might have potential benefits in the control of tumor metastasis during cancer therapy.