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After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma
BACKGROUND: The mechanism regarding rapid progression of residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily discussed. However, most studies have mainly focused on RFA-induced changes in the tumor cells. The present study was designed to d...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543343/ https://www.ncbi.nlm.nih.gov/pubmed/23171368 http://dx.doi.org/10.1186/1479-5876-10-230 |
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author | Kong, Jian Kong, Lingqun Kong, Jinge Ke, Shan Gao, Jun Ding, Xuemei Zheng, Lemin Sun, Huichuan Sun, Wenbing |
author_facet | Kong, Jian Kong, Lingqun Kong, Jinge Ke, Shan Gao, Jun Ding, Xuemei Zheng, Lemin Sun, Huichuan Sun, Wenbing |
author_sort | Kong, Jian |
collection | PubMed |
description | BACKGROUND: The mechanism regarding rapid progression of residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily discussed. However, most studies have mainly focused on RFA-induced changes in the tumor cells. The present study was designed to determine whether tumor-associated endothelial cells (TAECs) could contribute to the invasiveness of HCC after insufficient RFA. METHODS: TAECs were isolated from fresh HCC tissue and characterized. Morphological changes were observed in TAECs after heat treatment for 10 min. TAEC proliferation, migration and tube formation after heat treatment for 10 min at 37°C (control group), and 42 and 47°C (insufficient RFA groups) were examined. The differences in TAECs interactions with HepG2-GFP or HCCLM3-GFP cells among the two insufficient RFA groups and control group were evaluated. The expression of E-selectin, ICAM-1 and VCAM-1 in TAECs was measured. The effects of TAECs on the invasiveness of HepG2-GFP or HCCLM3-GFP cells after insufficient RFA were analyzed. The IL-6, IL-8, MCP-1 and GRO-α concentrations in conditioned medium from TAECs were measured after insufficient RFA. The associated signaling pathways of Akt, ERK1/2, STAT3 and NF-κB were analyzed in TAECs after insufficient RFA. RESULTS: TAECs expressed the EC-specific markers and took up complexes of Dil-Ac-LDL. Relative to the control group, the proliferation of TAECs was significantly inhibited and their migration and tube formation were significantly enhanced in the insufficient RFA groups. Significantly more HepG2-GFP or HCCLM3-GFP cells adhered to TACEs in these groups than in the control group (all P<0.001), via up-regulated expression of E-selectin, ICAM-1 and VCAM-1. TAECs promoted the invasiveness of HepG2-GFP or HCCLM3-GFP cells after insufficient RFA via the up-regulation of IL-6, IL-8, MCP-1 and GRO-α in conditioned medium (all P<0.05). Insufficient RFA enhanced the activities of Akt, ERK1/2 and NF-κB signaling pathways and inhibited STAT3 signaling pathways. CONCLUSIONS: Insufficient RFA enhanced TAEC migration and tube formation, and this may play a key role in the rapid growth of residual HCC. Increased expression of metastasis-related molecules in TAECs after insufficient RFA may be a potential mechanism for the metastasis of residual HCC. |
format | Online Article Text |
id | pubmed-3543343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35433432013-01-14 After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma Kong, Jian Kong, Lingqun Kong, Jinge Ke, Shan Gao, Jun Ding, Xuemei Zheng, Lemin Sun, Huichuan Sun, Wenbing J Transl Med Research BACKGROUND: The mechanism regarding rapid progression of residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily discussed. However, most studies have mainly focused on RFA-induced changes in the tumor cells. The present study was designed to determine whether tumor-associated endothelial cells (TAECs) could contribute to the invasiveness of HCC after insufficient RFA. METHODS: TAECs were isolated from fresh HCC tissue and characterized. Morphological changes were observed in TAECs after heat treatment for 10 min. TAEC proliferation, migration and tube formation after heat treatment for 10 min at 37°C (control group), and 42 and 47°C (insufficient RFA groups) were examined. The differences in TAECs interactions with HepG2-GFP or HCCLM3-GFP cells among the two insufficient RFA groups and control group were evaluated. The expression of E-selectin, ICAM-1 and VCAM-1 in TAECs was measured. The effects of TAECs on the invasiveness of HepG2-GFP or HCCLM3-GFP cells after insufficient RFA were analyzed. The IL-6, IL-8, MCP-1 and GRO-α concentrations in conditioned medium from TAECs were measured after insufficient RFA. The associated signaling pathways of Akt, ERK1/2, STAT3 and NF-κB were analyzed in TAECs after insufficient RFA. RESULTS: TAECs expressed the EC-specific markers and took up complexes of Dil-Ac-LDL. Relative to the control group, the proliferation of TAECs was significantly inhibited and their migration and tube formation were significantly enhanced in the insufficient RFA groups. Significantly more HepG2-GFP or HCCLM3-GFP cells adhered to TACEs in these groups than in the control group (all P<0.001), via up-regulated expression of E-selectin, ICAM-1 and VCAM-1. TAECs promoted the invasiveness of HepG2-GFP or HCCLM3-GFP cells after insufficient RFA via the up-regulation of IL-6, IL-8, MCP-1 and GRO-α in conditioned medium (all P<0.05). Insufficient RFA enhanced the activities of Akt, ERK1/2 and NF-κB signaling pathways and inhibited STAT3 signaling pathways. CONCLUSIONS: Insufficient RFA enhanced TAEC migration and tube formation, and this may play a key role in the rapid growth of residual HCC. Increased expression of metastasis-related molecules in TAECs after insufficient RFA may be a potential mechanism for the metastasis of residual HCC. BioMed Central 2012-11-21 /pmc/articles/PMC3543343/ /pubmed/23171368 http://dx.doi.org/10.1186/1479-5876-10-230 Text en Copyright ©2012 Kong et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Kong, Jian Kong, Lingqun Kong, Jinge Ke, Shan Gao, Jun Ding, Xuemei Zheng, Lemin Sun, Huichuan Sun, Wenbing After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma |
title | After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma |
title_full | After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma |
title_fullStr | After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma |
title_full_unstemmed | After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma |
title_short | After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma |
title_sort | after insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543343/ https://www.ncbi.nlm.nih.gov/pubmed/23171368 http://dx.doi.org/10.1186/1479-5876-10-230 |
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