TNF-α derived from M2 tumor-associated macrophages promotes epithelial-mesenchymal transition and cancer stemness through the Wnt/β-catenin pathway in SMMC-7721 hepatocellular carcinoma cells.

Autor: Chen Y; School of Medicine, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China., Wen H; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China; Guangzhou University of Traditional Chinese Medicine, Guangzhou 510000, China., Zhou C; School of Medicine, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China., Su Q; Laboratory Animal Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China., Lin Y; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China; Guangzhou University of Traditional Chinese Medicine, Guangzhou 510000, China., Xie Y; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510080, China., Huang Y; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China; Guangzhou University of Traditional Chinese Medicine, Guangzhou 510000, China., Qiu Q; School of Medicine, South China University of Technology, Guangzhou 510006, China., Lin J; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China., Huang X; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China., Tan W; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China., Min C; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China., Wang C; School of Medicine, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou 510080, China.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2019 May 01; Vol. 378 (1), pp. 41-50. Date of Electronic Publication: 2019 Mar 04.
DOI: 10.1016/j.yexcr.2019.03.005
Abstrakt: M2-polarized tumor-associated macrophages (M2-TAMs) infiltrating the tumor microenvironment contribute to hepatocellular carcinoma (HCC) progression. It was reported that cancer cells undergoing EMT will acquire stemness characteristics. Here, the HCC SMMC-7721 cell line was co-cultured with M2-TAMs polarized from THP-1 cells in vitro. In in vivo studies, we used nude mice subcutaneous tumor model to test whether the growth of the tumor was affected by M2-TAMs. Subsequently, EMT, stemness and Wnt/β-catenin pathway related markers were detected in cells and subcutaneous tumor tissues. TNF-α was also assessed in both the co-culture system supernatants and in nude mice serum. We found that SMMC-7721 underwent EMT and acquired stemness after co-culture with M2-TAMs, and resulted in larger tumor size following subcutaneous injection of SMMC-7721 suspended in M2-TAMs supernatants compared with SMMC-7721 alone. Enzyme linked immunosorbent assay showed that TNF-α expression was elevated in supernatants of M2-TAMs and positively correlated with tumor size in the serum of nude mice. Furthermore, we found that the Wnt/β-catenin pathway was a downstream target of TNF-α and that the Wnt/β-catenin inhibitor ICG-001 partially reversed EMT and attenuated cancer stemness. Our results indicate that TNF-α derived from M2-TAMs promote EMT and cancer stemness cells via the Wnt/β-catenin pathway.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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