Sorafenib inhibits macrophage-mediated epithelial-mesenchymal transition in hepatocellular carcinoma
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Yan-Ru Deng1,*, Wen-Bin Liu2,*, Zhe-Xiong Lian3, Xingsheng Li4, Xin Hou5
1Intensive Care Unit, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China
2Department of Hepatic Surgery and Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China
3Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei, China
4Department of Gerontology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
5Anhui Provincial Laboratory of Microbiology and Parasitology, Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, China
*These authors have contributed equally to this work
Xin Hou, email: [email protected]
Xingsheng Li, email: [email protected]
Keywords: hepatocellular carcinoma, epithelial-mesenchymal transition, sorafenib, HGF, Met
Received: March 27, 2016 Accepted: May 01, 2016 Published: May 18, 2016
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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