Downregulation Of TREM-1 Inhibits Liver Cancer Cell Function By Mediating Macrophages Polarization

Triggering receptor expressed on myeloid cells-1(TREM-1)is a protein expressed on tumor associated macrophages(TAMs),the predominant inflammatory cells in the tumor microenvironment;however,the mechanisms for TREM-1 influence on TAMs polarization during the progression of liver cancer have not been investigated.In the present study,Immunohistochemistry were used to detect the expression of TREM-1 in HCC and adjacent normal tissues.Human leukemia monocytic cell line(THP-1)were differentiated into M2 macrophages with phorbol 12-myristate 13-acetate(PMA)and IL-4,IL-13.A specific short-hairpin RNA(shRNA)was used for TREM-1 knockdown.To investigate the effects of downregulation of TREM-1 in macrophages during the migration and invasion of liver cancer cells,HepG2 and MHCC97 H cell lines were co-cultured with specific conditioned media(CM).Quantitative RT-PCR and Western blot analyses were used to detect M1 and M2 macrophages marker expression.Phosphoinositide 3-kinase(PI3K)/ Protein kinase B(AKT)signaling pathway protein expression was analyzed by Western blot.We found that the expressions of TREM-1 in HCC tissues were significantly higher than in adjacent normal tissues.We demonstrated that downregulation of TREM-1 in macrophages can shift M2 macrophages toward M1 phenotype,as defined by higher expression of M1 associated markers and lower expression of M2 associated markers.In addition,we found that downregulation of TREM-1 in macrophages suppressed migration and invasion of HepG2 and MHCC97 H cells.Furthermore,knock-down of TREM-1 in macrophages inhibited PI3K/AKT activation in the polarization of M2 macrophages.In conclusion,downregulation of TREM-1 expression in macrophages can shift M2 macrophages toward M1 phenotype and inhibit migration and invasion of HepG2 and MHCC97 H cells through PI3K/AKT signaling.These findings suggest TREM-1 is a novel potential therapeutic target for hepatocellular carcinoma(HCC)management.