Activated hepatic stellate cells promote angiogenesis in hepatocellular carcinoma by secreting angiopoietin-1.
J Cell Biochem
; 121(2): 1441-1451, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31609020
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
Carcinoma Hepatocelular
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Angiopoietina-1
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Células Estreladas do Fígado
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Neoplasias Hepáticas
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China