title: CD68(+)HLA-DR(+) M1-like macrophages promote motility of HCC cells via NF-κB/FAK pathway.
abstract: 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.
authors: Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan 250012, China.
authors: Hao
authors: H
authors: Wang
authors: Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan 250012, China.
authors: Xianteng
authors: X
authors: Wang
authors: Department of Internal Medicine, Jinan No. 1 People's Hospital, China.
authors: Xia
authors: X
authors: Li
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Yuchen
authors: Y
authors: Fan
authors: Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
authors: Guosheng
authors: G
authors: Li
authors: Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan 250012, China.
authors: Chun
authors: C
authors: Guo
authors: Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan 250012, China.
authors: Faliang
authors: F
authors: Zhu
authors: Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan 250012, China.
authors: Lining
authors: L
authors: Zhang
authors: Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan 250012, China. Electronic address: shiyongyu@sdu.edu.cn.
authors: Yongyu
authors: Y
authors: Shi
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000276:immunology / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051417:Focal Adhesion Kinase 1; D006684:HLA-DR Antigens; D016328:NF-kappa B; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496050:PTK2 protein, human
keywords: FAK; Hepatocellular carcinoma; NF-κB; Tumor-associated macrophage