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EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes
Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a primary estrogen-responsive gene that we previously identified in MCF-7 breast cancer cells using the CpG genomic binding-site cloning technique. The expression of EBAG9 protein is often upregulated in malignant tumors, suggesting...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259964/ https://www.ncbi.nlm.nih.gov/pubmed/25365482 http://dx.doi.org/10.1038/oncsis.2014.40 |
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author | Miyazaki, T Ikeda, K Horie-Inoue, K Kondo, T Takahashi, S Inoue, S |
author_facet | Miyazaki, T Ikeda, K Horie-Inoue, K Kondo, T Takahashi, S Inoue, S |
author_sort | Miyazaki, T |
collection | PubMed |
description | Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a primary estrogen-responsive gene that we previously identified in MCF-7 breast cancer cells using the CpG genomic binding-site cloning technique. The expression of EBAG9 protein is often upregulated in malignant tumors, suggesting that this protein is involved in cancer pathophysiology. In the present study, we investigated the role of EBAG9 in host defense against implanted tumors in Ebag9-knockout (Ebag9KO) mice. MB-49 mouse bladder cancer cells were subcutaneously implanted into Ebag9KO and control mice. We found that tumor formation and metastasis to the lung by MB-49 cells were substantially reduced in Ebag9KO mice compared with control mice. The infiltration of CD8(+), CD3(+) and CD4(+) T cells into the generated tumors was enhanced in Ebag9KO mice compared with controls. Notably, CD8(+) T cells isolated from tumors in Ebag9KO mice exhibited substantial upregulation of immunity- and chemoattraction-related genes, including interleukin-10 receptor, interferon gamma, granzyme A, granzyme B and chemokine (C-X-C motif) receptor 3 compared with CD8(+) T cells from tumors in control mice. The CD8(+) T cells isolated from tumors in Ebag9KO mice also exhibited enhanced degranulation and increased cytolytic activity. Furthermore, the adoptive transfer of CD8(+) T cells isolated from tumors in Ebag9KO host could repress tumor growth by MB-49 cells implanted in wild-type host. These results suggest that EBAG9 modulates tumor growth and metastasis by negatively regulating the adaptive immune response in host defense. EBAG9 could be a potential target for tumor immunotherapy. |
format | Online Article Text |
id | pubmed-4259964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42599642014-12-12 EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes Miyazaki, T Ikeda, K Horie-Inoue, K Kondo, T Takahashi, S Inoue, S Oncogenesis Original Article Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a primary estrogen-responsive gene that we previously identified in MCF-7 breast cancer cells using the CpG genomic binding-site cloning technique. The expression of EBAG9 protein is often upregulated in malignant tumors, suggesting that this protein is involved in cancer pathophysiology. In the present study, we investigated the role of EBAG9 in host defense against implanted tumors in Ebag9-knockout (Ebag9KO) mice. MB-49 mouse bladder cancer cells were subcutaneously implanted into Ebag9KO and control mice. We found that tumor formation and metastasis to the lung by MB-49 cells were substantially reduced in Ebag9KO mice compared with control mice. The infiltration of CD8(+), CD3(+) and CD4(+) T cells into the generated tumors was enhanced in Ebag9KO mice compared with controls. Notably, CD8(+) T cells isolated from tumors in Ebag9KO mice exhibited substantial upregulation of immunity- and chemoattraction-related genes, including interleukin-10 receptor, interferon gamma, granzyme A, granzyme B and chemokine (C-X-C motif) receptor 3 compared with CD8(+) T cells from tumors in control mice. The CD8(+) T cells isolated from tumors in Ebag9KO mice also exhibited enhanced degranulation and increased cytolytic activity. Furthermore, the adoptive transfer of CD8(+) T cells isolated from tumors in Ebag9KO host could repress tumor growth by MB-49 cells implanted in wild-type host. These results suggest that EBAG9 modulates tumor growth and metastasis by negatively regulating the adaptive immune response in host defense. EBAG9 could be a potential target for tumor immunotherapy. Nature Publishing Group 2014-11 2014-11-03 /pmc/articles/PMC4259964/ /pubmed/25365482 http://dx.doi.org/10.1038/oncsis.2014.40 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article Miyazaki, T Ikeda, K Horie-Inoue, K Kondo, T Takahashi, S Inoue, S EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes |
title | EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes |
title_full | EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes |
title_fullStr | EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes |
title_full_unstemmed | EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes |
title_short | EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes |
title_sort | ebag9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of t lymphocytes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259964/ https://www.ncbi.nlm.nih.gov/pubmed/25365482 http://dx.doi.org/10.1038/oncsis.2014.40 |
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