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Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition

BACKGROUND: Regulatory T (Treg) cells are a major component of the microenvironment of hepatocellular carcinoma (HCC) contributing to immunosuppression. The present study aimed to evaluate the effects of Treg cells on the invasion potential of HCC. METHODS: Infiltrating Treg cells were isolated from...

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Autores principales: Huang, Ai-Hua, Wang, Hong-Bo, Wu, Zhi-Feng, Wang, Yi-Hong, Hu, Bo, Jiang, Zhi-Nong, Jin, Mei, Wang, Lin-Bo, Gao, Ya-Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797764/
https://www.ncbi.nlm.nih.gov/pubmed/35116993
http://dx.doi.org/10.21037/tcr.2019.09.54
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author Huang, Ai-Hua
Wang, Hong-Bo
Wu, Zhi-Feng
Wang, Yi-Hong
Hu, Bo
Jiang, Zhi-Nong
Jin, Mei
Wang, Lin-Bo
Gao, Ya-Bo
author_facet Huang, Ai-Hua
Wang, Hong-Bo
Wu, Zhi-Feng
Wang, Yi-Hong
Hu, Bo
Jiang, Zhi-Nong
Jin, Mei
Wang, Lin-Bo
Gao, Ya-Bo
author_sort Huang, Ai-Hua
collection PubMed
description BACKGROUND: Regulatory T (Treg) cells are a major component of the microenvironment of hepatocellular carcinoma (HCC) contributing to immunosuppression. The present study aimed to evaluate the effects of Treg cells on the invasion potential of HCC. METHODS: Infiltrating Treg cells were isolated from fresh HCC tissues by immunomagnetic bead separation and detected by flow cytometry. Circulating tumor cells (CTCs) were detected using the CellSearch platform. The cell migration and invasion potentials were evaluated by Transwell assays. The cell viability was tested by the cell counting kit-8 (CCK8) approach, and the apoptosis rates were determined by flow cytometry. The concentrations of active transforming growth factor-β1 (TGFβ1) were measured by enzyme-linked immunosorbent assay. RESULTS: Infiltrating Treg cells significantly correlated with the number of CTCs and vascular invasion (both P<0.05). Moreover, these cells could greatly promote HCC migration, invasion, and proliferation, and inhibit HCC apoptosis. Polymerase chain reaction and Western blot assays revealed that Treg cells significantly decreased the expression levels of epithelium-related molecules and increased the expression levels of mesenchyme-related molecules. Treg cells could activate Smad2/3 via secreting TGFβ1, and these effects could be impaired by knocking down the expression of TGFβ1 in Treg cells. CONCLUSIONS: The involvement of infiltrating Treg cells in triggering the TGFβ1 signaling pathway and promoting the epithelial-mesenchymal transition (EMT) of cancer cells during tumor hematogenous dissemination is presumably responsible for increasing the invasiveness potential of HCC cells. Targeting Treg cells in microenvironments can be a promising therapeutic strategy to improve the prognosis for patients with HCC undergoing resection.
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spelling pubmed-87977642022-02-02 Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition Huang, Ai-Hua Wang, Hong-Bo Wu, Zhi-Feng Wang, Yi-Hong Hu, Bo Jiang, Zhi-Nong Jin, Mei Wang, Lin-Bo Gao, Ya-Bo Transl Cancer Res Original Article BACKGROUND: Regulatory T (Treg) cells are a major component of the microenvironment of hepatocellular carcinoma (HCC) contributing to immunosuppression. The present study aimed to evaluate the effects of Treg cells on the invasion potential of HCC. METHODS: Infiltrating Treg cells were isolated from fresh HCC tissues by immunomagnetic bead separation and detected by flow cytometry. Circulating tumor cells (CTCs) were detected using the CellSearch platform. The cell migration and invasion potentials were evaluated by Transwell assays. The cell viability was tested by the cell counting kit-8 (CCK8) approach, and the apoptosis rates were determined by flow cytometry. The concentrations of active transforming growth factor-β1 (TGFβ1) were measured by enzyme-linked immunosorbent assay. RESULTS: Infiltrating Treg cells significantly correlated with the number of CTCs and vascular invasion (both P<0.05). Moreover, these cells could greatly promote HCC migration, invasion, and proliferation, and inhibit HCC apoptosis. Polymerase chain reaction and Western blot assays revealed that Treg cells significantly decreased the expression levels of epithelium-related molecules and increased the expression levels of mesenchyme-related molecules. Treg cells could activate Smad2/3 via secreting TGFβ1, and these effects could be impaired by knocking down the expression of TGFβ1 in Treg cells. CONCLUSIONS: The involvement of infiltrating Treg cells in triggering the TGFβ1 signaling pathway and promoting the epithelial-mesenchymal transition (EMT) of cancer cells during tumor hematogenous dissemination is presumably responsible for increasing the invasiveness potential of HCC cells. Targeting Treg cells in microenvironments can be a promising therapeutic strategy to improve the prognosis for patients with HCC undergoing resection. AME Publishing Company 2019-10 /pmc/articles/PMC8797764/ /pubmed/35116993 http://dx.doi.org/10.21037/tcr.2019.09.54 Text en 2019 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Huang, Ai-Hua
Wang, Hong-Bo
Wu, Zhi-Feng
Wang, Yi-Hong
Hu, Bo
Jiang, Zhi-Nong
Jin, Mei
Wang, Lin-Bo
Gao, Ya-Bo
Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition
title Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition
title_full Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition
title_fullStr Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition
title_full_unstemmed Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition
title_short Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition
title_sort infiltrating regulatory t cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797764/
https://www.ncbi.nlm.nih.gov/pubmed/35116993
http://dx.doi.org/10.21037/tcr.2019.09.54
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