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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.
- Source :
-
Experimental cell research [Exp Cell Res] 2019 May 01; Vol. 378 (1), pp. 41-50. Date of Electronic Publication: 2019 Mar 04. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Carcinoma, Hepatocellular pathology
Cell Line, Tumor
Culture Media, Conditioned pharmacology
Humans
Liver Neoplasms pathology
Mice
Mice, Nude
Neoplastic Stem Cells drug effects
THP-1 Cells
Tumor Microenvironment
Tumor Necrosis Factor-alpha pharmacology
Carcinoma, Hepatocellular metabolism
Epithelial-Mesenchymal Transition
Liver Neoplasms metabolism
Macrophages metabolism
Neoplastic Stem Cells metabolism
Tumor Necrosis Factor-alpha metabolism
Wnt Signaling Pathway
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 378
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 30844387
- Full Text :
- https://doi.org/10.1016/j.yexcr.2019.03.005