期刊
CANCER BIOLOGY & THERAPY
卷 21, 期 11, 页码 1041-1050出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2020.1824478
关键词
Hepatocellular carcinoma; tumor-associated macrophages; TGF-beta 1; Gli2; IGF-II; ERK1; 2 signaling pathway; tumor growth
类别
资金
- National Natural Science Foundation of China [81660467]
- Natural Science Fund project of Jiangxi province [20171BAB215081]
Aim In this study, we explored the ability of TAMs to affect the malignant phenotype of human hepatoma Huh-7 cells through the Gli2/IGF-II/ERK1/2 pathway. Methods The TAMs were characterized by flow cytometry and ELISA assays. Huh-7 cells were treated with conditioned medium of TAMs (TAMs-CM), and the proliferation, migration and invasion abilities were measured by CCK-8, Transwell and scratch assays. The levels of TGF-beta 1, Gli2, IGF-II and related proteins in the ERK1/2 pathway and the epithelial-mesenchymal transition (EMT) process were examined by RT-qPCR and western blot. Huh-7 cells were injected subcutaneously into nude mice with TAMs to explore the role of TAMs in tumor growth. Results The expression levels of TGF-beta 1, Gli2 and IGF-II and the cell proliferation, migration and invasion abilities were elevated in Huh-7 cells treated with TAMs-CM. TGF-beta 1 was upregulated in the conditioned medium and was found to be involved in the promotion of migration, invasion and the EMT of Huh-7 cells. The activation of TGF-beta 1 signaling increased the expression of Gli2. Knockdown of Gli2 decreased the expression of IGF-II and also reversed the promotional effect of the conditioned medium on migration, invasion and the EMT of Huh-7 cells. TGF-beta 1/Gli2/IGF-II signaling was shown to promote the malignant phenotype of Huh-7 cells by activating the ERK1/2 signaling pathway. Further, TGF-beta 1 knockdown attenuated the influence of TAMs on tumor growth in mouse model. Conclusion The TGF-beta 1 secreted by TAMs promotes the migration, invasion and EMT of human hepatoma Huh-7 cells through the Gli2/IGF-II/ERK1/2 pathway.
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