Colon cancer-derived factors activate NF-κB in myeloid cells via TLR2 to link inflammation and tumorigenesis
Colon cancer-derived factors activate NF-κB in myeloid cells via TLR2 to link inflammation and tumorigenesis
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DOI：
10.3892/mmr.2011.545
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发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Akanuma, Masao
中科院分区：
文献类型：
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作者：
Maeda, Shin;Hikiba, Yohko;Akanuma, Masao
结肠癌发生过程中NF-κ B B活化的确切机制尚不清楚。本研究旨在确定结肠癌细胞诱导炎症反应的方式，以联系肿瘤生长。用来自几种结肠癌细胞系的上清液的培养基刺激巨噬细胞。在用显示组成型NF-κ B活性的肿瘤细胞上清液刺激的样品中观察到巨噬细胞积聚和NF-κ B活化。受刺激的巨噬细胞中NF-κ B的活化依赖于TLR 2和IKK β，而不是TLR 4。各种细胞因子，如IL-6，以TLR 2依赖的方式诱导。用最初用肿瘤细胞培养基刺激的巨噬细胞的上清液培养的肿瘤细胞比用未刺激的巨噬细胞的上清液刺激的那些生长得更快。总之，结肠癌衍生因子通过TLR 2依赖性机制诱导巨噬细胞的积累并激活NF-κ B，表明炎症和肿瘤生长之间存在重要联系。
The exact mechanism for the contribution of NF-kappa B activation during colon carcinogenesis is unclear. The present study aimed to determine the manner in which colon cancer cells induce inflammatory responses in order to link tumor growth. Macrophages were stimulated with cultured medium from the supernatants of several colon cancer cell lines. Macrophage accumulation and NF-kappa B activation were observed in samples that were stimulated with supernatant from tumor cells that showed constitutive NF-kappa B activity. NF-kappa B activation in the stimulated macrophages was dependent on TLR2 and IKK beta, but not TLR4. Various cytokines, such as IL-6, were induced in a TLR2-dependent manner. Tumor cells that were cultured with the supernatant of macrophages originally stimulated with the tumor cell cultured media grew more rapidly than those stimulated with the supernatant of unstimulated macrophages. Taken together, colon cancer-derived factors induce the accumulation of macrophages and activate NF-kappa B through a TLR2-dependent mechanism, suggesting an important link between inflammation and tumor growth.