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Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma
BACKGROUND: Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear. METHODS: The effect of IFN-α treatment was studied by using an orthotopic xenograft model...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601095/ https://www.ncbi.nlm.nih.gov/pubmed/23527047 http://dx.doi.org/10.1371/journal.pone.0058913 |
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author | Zhuang, Peng-Yuan Shen, Jun Zhu, Xiao-Dong Zhang, Ju-Bo Tang, Zhao-You Qin, Lun-Xiu Sun, Hui-Chuan |
author_facet | Zhuang, Peng-Yuan Shen, Jun Zhu, Xiao-Dong Zhang, Ju-Bo Tang, Zhao-You Qin, Lun-Xiu Sun, Hui-Chuan |
author_sort | Zhuang, Peng-Yuan |
collection | PubMed |
description | BACKGROUND: Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear. METHODS: The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry. RESULTS: IFN-α treatment did not decrease the number of CTCs (0.075%±0.020% versus 0.063%±0.018%, P = 0.574, IFN-α–treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75±1.0 versus 28.0±6.3, P = 0.008; size [pixels]: 116.8±72.2 versus 5226.4±1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%±0.04% versus 1.36%±0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1±1.7 versus 21.9±0.4, P<0.000) in the lung, which was independent of the primary tumor. CONCLUSION: IFN-α inhibited lung metastasis by directly modulating the lung microenvironment. |
format | Online Article Text |
id | pubmed-3601095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36010952013-03-22 Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma Zhuang, Peng-Yuan Shen, Jun Zhu, Xiao-Dong Zhang, Ju-Bo Tang, Zhao-You Qin, Lun-Xiu Sun, Hui-Chuan PLoS One Research Article BACKGROUND: Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear. METHODS: The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry. RESULTS: IFN-α treatment did not decrease the number of CTCs (0.075%±0.020% versus 0.063%±0.018%, P = 0.574, IFN-α–treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75±1.0 versus 28.0±6.3, P = 0.008; size [pixels]: 116.8±72.2 versus 5226.4±1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%±0.04% versus 1.36%±0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1±1.7 versus 21.9±0.4, P<0.000) in the lung, which was independent of the primary tumor. CONCLUSION: IFN-α inhibited lung metastasis by directly modulating the lung microenvironment. Public Library of Science 2013-03-18 /pmc/articles/PMC3601095/ /pubmed/23527047 http://dx.doi.org/10.1371/journal.pone.0058913 Text en © 2013 Zhuang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhuang, Peng-Yuan Shen, Jun Zhu, Xiao-Dong Zhang, Ju-Bo Tang, Zhao-You Qin, Lun-Xiu Sun, Hui-Chuan Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma |
title | Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma |
title_full | Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma |
title_fullStr | Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma |
title_full_unstemmed | Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma |
title_short | Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma |
title_sort | direct transformation of lung microenvironment by interferon-α treatment counteracts growth of lung metastasis of hepatocellular carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601095/ https://www.ncbi.nlm.nih.gov/pubmed/23527047 http://dx.doi.org/10.1371/journal.pone.0058913 |
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