Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer cells through NF-B activation
Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer cells through NF-B activation
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DOI：
10.1002/mc.22750
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发表时间：
2018-02-01
影响因子：
4.6
通讯作者：
Song, Yong Sang
中科院分区：
文献类型：
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作者：
Cho, Untack;Kim, Boyun;Song, Yong Sang
肥胖是一个严重的健康问题，并且与癌症的不良预后密切相关，可能是通过诱发慢性炎症而导致的。据推测，肥胖导致癌症进展的罪魁祸首是巨噬细胞。已经观察到由于肥胖引起的慢性炎症导致脂肪组织中巨噬细胞的积累。然而，肥胖引起的巨噬细胞积累与卵巢癌进展相关仍不清楚。因此，需要进一步明确巨噬细胞在癌症进展中的作用以进行治疗干预。在这里，我们确定了 1 型巨噬细胞（M1 巨噬细胞）对卵巢癌细胞与转移的影响。本研究使用卵巢癌细胞系（PA-1、SKOV3）和单核细胞源性巨噬细胞。用 M1 巨噬细胞条件培养基处理卵巢癌细胞可增加转移潜力，例如迁移和侵袭能力。有趣的是，用 M1 巨噬细胞条件培养基处理后，NF-B、p60 和 p50 从细胞质中的核转位得到增强，同时 NF-B 的转录活性也增加。用 TPCK（NF-B 抑制剂）和 NF-B siRNA 对卵巢癌细胞进行预处理，可抑制 M1 巨噬细胞诱导的转移潜能。此外，TNF-α对卵巢癌细胞的治疗显示出NF-B的激活。 TNF-抑制剂、依那西普和 M1 巨噬细胞条件培养基对卵巢癌细胞系的共同处理逆转了 M1 巨噬细胞条件培养基诱导的 NF-B 激活。总而言之，M1巨噬细胞释放的TNF-α通过激活NF-B信号通路增加了卵巢癌细胞的转移潜力。这些结果为 M1 巨噬细胞在卵巢癌肿瘤微环境中的关键作用提供了新的见解。
Obesity is a serious health problem and critically related to poor prognosis in cancer, presumably through induction of chronic inflammation. The major culprit for cancer progression in obesity is presumed to be macrophages. Accumulation of macrophages in adipose tissue due to obesity induced chronic inflammation has been observed. However, obesity-induced macrophage accumulation related to ovarian cancer progression remains unclear. So, the role of macrophage in cancer progression is needed to be further defined for therapeutic intervention. Here we determined the effect of macrophage type 1 (M1 macrophage) on ovarian cancer cells in relation to the metastasis. Ovarian cancer cell lines (PA-1, SKOV3) and monocyte-derived macrophages were used in this study. Treatment with M1 macrophage conditioned media on ovarian cancer cells increased the metastatic potential, such as migration and invasion capabilities. Interestingly, upon treatment with M1 macrophage conditioned media, nuclear translocation of NF-B, p60, and p50, from the cytosol was enhanced together with increased transcriptional activity of the NF-B. Pre-treatment with TPCK (NF-B inhibitor) and NF-B siRNA on ovarian cancer cells suppressed M1 macrophage-induced metastatic potential. Furthermore, Treatment of TNF- on ovarian cancer cells showed NF-B activation. Co-treatment with TNF- inhibitor, etanercept, and M1 macrophage conditioned media on ovarian cancer cell lines reversed M1 macrophage conditioned media induced NF-B activation. Taken together, TNF- released from M1 macrophage increased metastatic potential in ovarian cancer cells through the activation of NF-B signaling pathway. These results provide a new insight into the critical role of M1 macrophage in the tumor microenvironment in ovarian cancer.