Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma

• Published in: Journal of hepatology 2015-03, Vol.62 (3), p.607-616
• Main Authors: Yeung, Oscar W.H, Lo, Chung-Mau, Ling, Chang-Chun, Qi, Xiang, Geng, Wei, Li, Chang-Xian, Ng, Kevin T.P, Forbes, Stuart J, Guan, Xin-Yuan, Poon, Ronnie T.P, Fan, Sheung-Tat, Man, Kwan
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - secondary; Cell Line; Cell Line, Tumor; Cell Proliferation; Chemokine CCL22 - metabolism; Coculture Techniques; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - immunology; Female; Gastroenterology and Hepatology; Hepatocellular carcinoma; Heterografts; Humans; Invasiveness; Liver Neoplasms - immunology; Liver Neoplasms - pathology; M2 macrophages; Macrophage Activation; Macrophages - classification; Macrophages - immunology; Male; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Invasiveness - immunology; Neoplasm Invasiveness - pathology; Prognosis; Prognostic predictor; Receptors, CCR4 - metabolism; Receptors, Cell Surface - metabolism; Scavenger Receptors, Class A - metabolism; Young Adult
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2014.10.029

Background & Aims The roles of alternatively activated (M2) macrophages on pro-tumour phenotypes have been well documented in many cancers except hepatocellular carcinoma (HCC). Considering their close relationship with chronic tissue injuries as well as enhanced tumour invasiveness and growth, we aimed to investigate the direct effects of M2 macrophages on HCC. Methods M2 macrophages in 95 HCC clinical specimens were quantified using immunohistochemistry and quantitative PCR. The pro-tumour functions and the underlying molecular mechanisms of M2 macrophages in HCC were investigated in vivo and in an in vitro co-culture system. Results In the clinical study, high M2-specific CD163 (hazard ratio = 2.693; p = 0.043) and scavenger receptor A (hazard ratio = 3.563; p = 0.044) levels indicated poor prognosis and correlated with increased tumour nodules and venous infiltration in HCC patients. In an orthotopic model, the liver tumour volume was increased 3.26-fold (1.27 cm3 ± 0.36) after M2 macrophage injection compared with the control (0.39 cm3 ± 0.05) ( p = 0.032). An increased rate of lung metastasis was also found in the treatment group. In vitro , co-cultivation with M2 macrophages elevated the number of HCC cells (MHCC97L) and migration events by 1.3-fold and 3.2-fold, respectively ( p