Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan 250012, China.
Department of Internal Medicine, Jinan No. 1 People's Hospital, China.
Cancer Lett. 2014 Apr 1;345(1):91-9. doi: 10.1016/j.canlet.2013.11.013. Epub 2013 Dec 11.
TAM is a prominent component of inflammatory microenvironment, presenting M1 and M2 polarized states in HCC. The objective of this study is to investigate the relationship between M1-polarized macrophages and metastasis in HCC. We used immunohistochemical double-staining method to inspect the infiltration of CD68(+)HLA-DR(+) M1-like macrophages in HCC tissues. The M1-polarized macrophage was derived from THP-1 cell treated by LPS and IFN-γ in vitro. Transwell migration assay was used to evaluate whether the M1-polarized macrophage enhanced motility of HCC cells in the presence or absence of NF-κB inhibitor Bay 11-7802. The activation of NF-κB and FAK signaling pathways was examined by Western blot assay. Our results showed that the density of CD68(+)HLA-DR(+) TAM in the HCC with metastasis is significantly higher than that in the HCC without metastasis. Moreover, the conditioned medium from the M1 macrophages promote the migration of HCC cells and induced the activation of NF-κB and FAK signaling. The promoted migration of HCC cells was abrogated by the Bay 11-7802, as well as the activation of NF-κB and FAK pathway. Our findings implied a pro-metastatic role of M1-like TAM in HCC.
TAM 是炎症微环境的重要组成部分，在 HCC 中呈现 M1 和 M2 极化状态。本研究旨在探讨 HCC 中 M1 极化巨噬细胞与转移的关系。我们使用免疫组化双重染色法检测 HCC 组织中 CD68(+)HLA-DR(+)M1 样巨噬细胞的浸润。M1 极化巨噬细胞来源于 LPS 和 IFN-γ体外处理的 THP-1 细胞。Transwell 迁移实验用于评估在存在或不存在 NF-κB 抑制剂 Bay 11-7802 的情况下，M1 极化巨噬细胞是否增强 HCC 细胞的迁移能力。通过 Western blot 检测 NF-κB 和 FAK 信号通路的激活情况。我们的结果表明，有转移的 HCC 中 CD68(+)HLA-DR(+)TAM 的密度明显高于无转移的 HCC。此外，M1 巨噬细胞的条件培养基促进 HCC 细胞的迁移，并诱导 NF-κB 和 FAK 信号通路的激活。Bay 11-7802 以及 NF-κB 和 FAK 通路的激活均可阻断 HCC 细胞的迁移。我们的研究结果表明，M1 样 TAM 在 HCC 中具有促转移作用。
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