CD68+HLA-DR+ M1-like macrophages promote motility of HCC cells via NF-κB/FAK pathway

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-gamma 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-kappa B inhibitor Bay 11-7802. The activation of NF-kappa B 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-kappa B and FAR signaling. The promoted migration of HCC cells was abrogated by the Bay 11-7802, as well as the activation of NF-kappa B and FAR pathway. Our findings implied a pro-metastatic role of M1-like TAM in HCC. (C) 2013 Elsevier Ireland Ltd. All rights reserved.