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B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival
Aberrant expression of B7-H4 occurs across a broad spectrum of human cancers. The aim of this study was to investigate the key role of B7-H4 during tumorigenesis and metastasis of human lung cancer. Our data showed that the shRNA-mediated disruption of B7-H4 markedly inhibited tumor cell proliferati...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386653/ https://www.ncbi.nlm.nih.gov/pubmed/28061481 http://dx.doi.org/10.18632/oncotarget.14475 |
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author | Zhang, Xiuqin Cai, Liming Zhang, Guangbo Shen, Yu Huang, Jianan |
author_facet | Zhang, Xiuqin Cai, Liming Zhang, Guangbo Shen, Yu Huang, Jianan |
author_sort | Zhang, Xiuqin |
collection | PubMed |
description | Aberrant expression of B7-H4 occurs across a broad spectrum of human cancers. The aim of this study was to investigate the key role of B7-H4 during tumorigenesis and metastasis of human lung cancer. Our data showed that the shRNA-mediated disruption of B7-H4 markedly inhibited tumor cell proliferation, invasion and migration, increased cell apoptosis and arrested cell cycle at G0/G1. These changes were accompanied by a marked increase in Bax and caspase-3/caspase-8, but a decrease in Bcl-2, cyclinD1 and activation of AKT. In addition, our shRNA-mediated disruption of B7-H4 led to a marked decrease in tumor growth in the immune-compromised mice. Importantly, B7-H4 was expressed in 53.33% of lung carcinomas from our patient cohort (n = 90), but not in any of adjacent non-cancerous tissues, according to our IHC analyses. In particular, B7-H4 expression appeared to be associated with lymph node metastasis (P = 0.008) and TNM stage (P = 0.012). Taken together, our study demonstrates a strong promoting role of B7-H4 in lung tumor growth, progression and metastasis, and supports its potential as a therapeutic target for the treatment of the disease. |
format | Online Article Text |
id | pubmed-5386653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53866532017-04-26 B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival Zhang, Xiuqin Cai, Liming Zhang, Guangbo Shen, Yu Huang, Jianan Oncotarget Research Paper Aberrant expression of B7-H4 occurs across a broad spectrum of human cancers. The aim of this study was to investigate the key role of B7-H4 during tumorigenesis and metastasis of human lung cancer. Our data showed that the shRNA-mediated disruption of B7-H4 markedly inhibited tumor cell proliferation, invasion and migration, increased cell apoptosis and arrested cell cycle at G0/G1. These changes were accompanied by a marked increase in Bax and caspase-3/caspase-8, but a decrease in Bcl-2, cyclinD1 and activation of AKT. In addition, our shRNA-mediated disruption of B7-H4 led to a marked decrease in tumor growth in the immune-compromised mice. Importantly, B7-H4 was expressed in 53.33% of lung carcinomas from our patient cohort (n = 90), but not in any of adjacent non-cancerous tissues, according to our IHC analyses. In particular, B7-H4 expression appeared to be associated with lymph node metastasis (P = 0.008) and TNM stage (P = 0.012). Taken together, our study demonstrates a strong promoting role of B7-H4 in lung tumor growth, progression and metastasis, and supports its potential as a therapeutic target for the treatment of the disease. Impact Journals LLC 2017-01-03 /pmc/articles/PMC5386653/ /pubmed/28061481 http://dx.doi.org/10.18632/oncotarget.14475 Text en Copyright: © 2017 Zhang et al. http://creativecommons.org/licenses/by/3.0/ 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 credited. |
spellingShingle | Research Paper Zhang, Xiuqin Cai, Liming Zhang, Guangbo Shen, Yu Huang, Jianan B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival |
title | B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival |
title_full | B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival |
title_fullStr | B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival |
title_full_unstemmed | B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival |
title_short | B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival |
title_sort | b7-h4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386653/ https://www.ncbi.nlm.nih.gov/pubmed/28061481 http://dx.doi.org/10.18632/oncotarget.14475 |
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