期刊
ONCOTARGET
卷 7, 期 25, 页码 38292-38305出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9438
关键词
hepatocellular carcinoma; epithelial-mesenchymal transition; sorafenib; HGF; met
资金
- National Basic Research Program of China (973 Program) [2010CB945300, 2013CB944900]
- National Natural Science Foundation of China [81402474, 81571540, 81272398]
- Anhui Provincial Natural Science Foundation [1508085QH169, 1408085MKL71]
- Chongqing Natural Science Foundation [cstc2012jjA10088]
Tumor-associated macrophages, crucial components of the microenvironment in hepatocellular carcinoma, hamper anti-cancer immune responses. The aim of the present study was to investigate the effect of sorafenib on the formation of the tumor microenvironment, especially the relationship between polarized macrophages and hepatocytes. Macrophage infiltration was reduced in patients with hepatocellular carcinoma who were treated with sorafenib. In vitro, sorafenib abolished polarized macrophage-induced epithelial mesenchymal transition (EMT) and migration of hepatocellular carcinoma cells but not normal hepatocytes. Moreover, sorafenib attenuated HGF secretion in polarized macrophages, and decreased plasma HGF in patients with hepatocellular carcinoma. Additionally, sorafenib abolished the polarized macrophage-induced activation of the HGF receptor Met in hepatocellular carcinoma cells. Our findings suggest that sorafenib inhibits polarized macrophage-induced EMT in hepatocellular carcinoma cells via the HGF-Met signaling pathway. These results contribute to our understanding of the immunological mechanisms that underlie the protective effects of sorafenib in hepatocellular carcinoma therapy.
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