Sorafenib inhibits macrophage-mediated epithelial-mesenchymal transition in hepatocellular carcinoma

被引：44

作者：

Deng, Yan-Ru ^{[1
]}

Liu, Wen-Bin ^{[2
,3
]}

Lian, Zhe-Xiong ^{[4
,5
]}

Li, Xingsheng ^{[6
]}

Hou, Xin ^{[7
]}

机构：

[1] Anhui Med Univ, Affiliated Prov Hosp, Intens Care Unit, Hefei, Peoples R China

[2] Anhui Med Univ, Affiliated Prov Hosp, Dept Hepat Surg, Hefei, Peoples R China

[3] Anhui Med Univ, Affiliated Prov Hosp, Anhui Prov Key Lab Hepatopancreatobiliary Surg, Hefei, Peoples R China

[4] Univ Sci & Technol China, Inst Immunol, Liver Immunol Lab, Hefei 230026, Peoples R China

[5] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China

[6] Chongqing Med Univ, Dept Gerontol, Affiliated Hosp 2, Chongqing, Peoples R China

[7] Anhui Med Univ, Dept Microbiol & Parasitol, Anhui Prov Lab Microbiol & Parasitol, Hefei, Anhui, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 25期

基金：

中国国家自然科学基金;

关键词：

hepatocellular carcinoma; epithelial-mesenchymal transition; sorafenib; HGF; met; TUMOR-ASSOCIATED MACROPHAGES; HEPATOCYTE GROWTH-FACTOR; MICROENVIRONMENTAL REGULATION; BETA-CATENIN; CANCER CELLS; PROGRESSION; EXPRESSION; RECEPTOR; EMT; SURVIVAL;

D O I：

10.18632/oncotarget.9438

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：38292 / 38305

页数：14

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