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Activated hepatic stellate cells promote angiogenesis in hepatocellular carcinoma by secreting angiopoietin‐1
Author(s) -
Lin Nan,
Meng Lili,
Lin Jizong,
Chen Shuxian,
Zhang Peng,
Chen Qilong,
Lin Yang
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29380
Subject(s) - angiogenesis , hepatic stellate cell , cd34 , cancer research , stromal cell , hepatocellular carcinoma , angiopoietin , vascular endothelial growth factor , biology , pathology , medicine , microbiology and biotechnology , stem cell , vegf receptors
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.