Lipopolysaccharide promotes angiogenesis in mice model of HCC by stimulating hepatic stellate cell activation via TLR4 pathway.

Yi Lu,Shuxian Chen,Zheng Zhou,Nan Lin,Jianliang Xu

doi:10.1093/abbs/gmx100

Abstract

Angiogenesis plays a key role in the progression of hepatocellular carcinoma (HCC). This study aimed to investigate whether lipopolysaccharide (LPS) could promote HCC angiogenesis and the role of hepatic stellate cell (HSC) in this process. In vivo orthotopic HCC model and the effect of LPS on HSC in vitro were studied. Our results demonstrated that LPS-induced HSC activation during the promotion of HCC growth and angiogenesis in mice. The LPS-TLR4 (Toll-like receptor 4) pathway in HSC is responsible for HCC angiogenesis. LPS-induced secretion of pro-angiogenic factors from HSC could promote endothelial cell migration and tubulogenesis. This study suggests that LPS acts with HSC in tumor stroma and promotes the secretion of pro-angiogenic factors that increase angiogenesis in HCC.

Highlights

Hepatocellular carcinoma (HCC) is a severe malignant tumor and the third most common cause of death from cancers worldwide [1]
In order to determine the effect of LPS on HCC growth and angiogenesis, the mice model of HCC was established by using H22 and Hepatic stellate cell (HSC)-T6 cells and intrahepatic mixed injection method, mice were injected with 50 μg LPS or saline for duration of 1 week
To investigate whether HCC growth and vascular change are associated with HSC, mice tumor samples in both groups were analyzed for α-SMA, a marker for activated HSC. α-SMA was highly expressed in tumor stroma exposed to LPS (Fig. 2)

Summary

Introduction

Hepatocellular carcinoma (HCC) is a severe malignant tumor and the third most common cause of death from cancers worldwide [1]. ~20% of HCC patients have the option of curative resection, there is still a high incidence of postoperative recurrence and metastasis for this fatal disease [2]. The liver microenvironment contributes to HCC progression [3,4]. Hepatic stellate cell (HSC) is an identified feature of liver cirrhosis and plays a key role in HCC microenvironment [6,7,8]. It has been found that HSC is associated with HCC angiogenesis [9]. HSC secretes angiogenic factors that play a critical role in HCC initiation, progression and metastasis, as well as in the creation of new vessels [10,11,12], but the mechanism is still unclear

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