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The role of GAGE cancer/testis antigen in metastasis: the jury is still out

BACKGROUND: GAGE cancer/testis antigens are frequently expressed in various types of malignancies and represent attractive targets for immunotherapy, however their role in cancer initiation and progression has remained elusive. GAGE proteins are expressed in normal cells during early development wit...

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Autores principales: Gjerstorff, Morten Frier, Terp, Mikkel Green, Hansen, Malene Bredahl, Ditzel, Henrik Jørn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706694/
https://www.ncbi.nlm.nih.gov/pubmed/26747105
http://dx.doi.org/10.1186/s12885-015-1998-y
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author Gjerstorff, Morten Frier
Terp, Mikkel Green
Hansen, Malene Bredahl
Ditzel, Henrik Jørn
author_facet Gjerstorff, Morten Frier
Terp, Mikkel Green
Hansen, Malene Bredahl
Ditzel, Henrik Jørn
author_sort Gjerstorff, Morten Frier
collection PubMed
description BACKGROUND: GAGE cancer/testis antigens are frequently expressed in various types of malignancies and represent attractive targets for immunotherapy, however their role in cancer initiation and progression has remained elusive. GAGE proteins are expressed in normal cells during early development with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model. METHODS: We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell lines, which are equally tumorigenic in immunodeficient mice, but differ with their ability to generate metastases in the lungs and lymph nodes. RESULTS: Although GAGE proteins were strongly upregulated in the highly metastatic clone (CL16) compared to non-metastatic (NM2C5), weakly metastatic (M4A4) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further studies are needed to clarify the contribution of GAGE proteins to the metastatic potential of different types of cancer cells.
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spelling pubmed-47066942016-01-10 The role of GAGE cancer/testis antigen in metastasis: the jury is still out Gjerstorff, Morten Frier Terp, Mikkel Green Hansen, Malene Bredahl Ditzel, Henrik Jørn BMC Cancer Research Article BACKGROUND: GAGE cancer/testis antigens are frequently expressed in various types of malignancies and represent attractive targets for immunotherapy, however their role in cancer initiation and progression has remained elusive. GAGE proteins are expressed in normal cells during early development with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model. METHODS: We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell lines, which are equally tumorigenic in immunodeficient mice, but differ with their ability to generate metastases in the lungs and lymph nodes. RESULTS: Although GAGE proteins were strongly upregulated in the highly metastatic clone (CL16) compared to non-metastatic (NM2C5), weakly metastatic (M4A4) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further studies are needed to clarify the contribution of GAGE proteins to the metastatic potential of different types of cancer cells. BioMed Central 2016-01-08 /pmc/articles/PMC4706694/ /pubmed/26747105 http://dx.doi.org/10.1186/s12885-015-1998-y Text en © Gjerstorff et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gjerstorff, Morten Frier
Terp, Mikkel Green
Hansen, Malene Bredahl
Ditzel, Henrik Jørn
The role of GAGE cancer/testis antigen in metastasis: the jury is still out
title The role of GAGE cancer/testis antigen in metastasis: the jury is still out
title_full The role of GAGE cancer/testis antigen in metastasis: the jury is still out
title_fullStr The role of GAGE cancer/testis antigen in metastasis: the jury is still out
title_full_unstemmed The role of GAGE cancer/testis antigen in metastasis: the jury is still out
title_short The role of GAGE cancer/testis antigen in metastasis: the jury is still out
title_sort role of gage cancer/testis antigen in metastasis: the jury is still out
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706694/
https://www.ncbi.nlm.nih.gov/pubmed/26747105
http://dx.doi.org/10.1186/s12885-015-1998-y
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