The effects of monoacylglycerol lipase on M2-like tumor-associated macrophages-induced lung metastasis of MHCC97H cells

Abstract

Objective To investigate the effects of monoacylglycerol lipase on M2-like tumor-associated macrophages (TAMs)-induced lung metastasis of MHCC97H cells. Methods M2-like TAMs were induced from THP-1 cells, and identified by flow cytometry. The expression of MAGL in M2-like TAMs were down-regulated or up-regulated by MAGL inhibitor JZL184 or MAGL plasmid transfection, respectively. The mRNA of MAGL expression in each group were detected by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). The experimental model of MHCC97H pulmonary metastasis in mice was established by tail vein injection. The fluorescence intensity of pulmonary metastasis in mice were measured by in vivo fluorescence imaging system. Results THP-1 cells were successfully induced to M2-like TAMs. The different expression of MAGL in M2-like TAMs were successfully established, and significant differences among each groups were verified by RT-PCR (TAMs-WT vs. TAMs-WT+ JZL184: t=6.221, P<0.01; TAMs-WT+ JZL184 vs. TAMs-MAGL-OE+ JZL184: t=5.456, P<0.01). The lung metastasis model of mice showed that JZL184-treated M2-like TAMs significantly promoted the lung fluorescence intensity of MHCC97H mice compared to that of non-intervention group [(0.980±0.140)×104 a. u. vs. (0.558±0.082)×104 a. u. ; t=4.497, P<0.05]. Nevertheless, these JZL184-induced effects could markedly be reversed by up-regulation of MAGL expression in M2-like TAMs [(0.571±0.077)×104 a. u. ; t=4.429, P<0.05]. Conclusion The reduced expression of MAGL in M2-like TAMs promotes lung metastasis of MHCC97H cells. Key words: Hepatocellular carcinoma; Tumor-associated macrophages; Monoacylglycerol lipase