Activated hepatic stellate cells promote angiogenesis in hepatocellular carcinoma by secreting angiopoietin‐1. Issue 2 (14th October 2019)

• Record Type: Journal Article
• Authors: Lin, Nan; Meng, Lili; Lin, Jizong; Chen, Shuxian; Zhang, Peng; Chen, Qilong; Lin, Yang
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 2(2020)
• Page Start: 1441
• Page End: 1451
• Publication Date: 2019-10-14
• Subjects: activated hepatic stellate cells -- angiogenesis -- angiopoietin‐1 -- hepatic cellular carcinoma; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29380
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Angiogenesis is the central pathological process in hepatocellular carcinoma (HCC), and its progression is affected by tumor cells and the microenvironment. Activated hepatic stellate cells (aHSCs) are the most significant stromal cells involved in HCC. This study was aimed to explore the effects and mechanisms of aHSCs on angiogenesis in HCC. We isolated primary hepatoma cells, aHSCs, and hepatic vascular endothelial cells from human HCC samples. Then, we performed a novel in vitro assay and in vivo experiment in a nude mouse HCC model to investigate the functions of aHSCs on angiogenesis in HCC. Our results demonstrated that aHSCs are the primary sources of angiopoietin‐1 (Ang‐1) in human HCC in vitro, and aHSCs could promote hepatic vascular endothelial cell (HVEC) growth by secreting Ang‐1. Furthermore, aHSCs could induce HVEC microtubule formation, and this ability was reduced when Ang‐1 expression was silenced in aHSCs. In addition, CD34 expression in a nude mouse HCC model was downregulated when Ang‐1 messenger RNA was silenced in aHSCs. Our data also indicated that HSC Ang‐1 expression could be inhibited by overexpressing Raf kinase inhibitor protein. Therefore, we suggest that aHSCs promote angiogenesis through secreting Ang‐1, potentially providing an interesting target for antiangiogenic therapies for HCC. Abstract : The aim of this study was to assess the effects of aHSCs on angiogenesis and growth of HCC in vitro and in vivo. Our experiments showed that aHSCs are the primary sources of Ang‐1 in human HCC, which might induce proliferation and microtubule formation of hepatic vascular endothelial cells (HVECs) by secreting Ang‐1 in vitro. The aHSCs might also promote the growth and angiogenesis of human HCC via Ang‐1 in a nude mouse model.