Cargando…

The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors

Identification of novel tumor-specific targets is important for the future development of immunotherapeutic strategies using genetically engineered T cells or vaccines. In this study, we characterized the expression of VCX2, a member of the VCX/Y cancer/testis antigen family, in a large panel of nor...

Descripción completa

Detalles Bibliográficos
Autores principales: Jakobsen, Mie K., Traynor, Sofie, Stæhr, Mette, Duijf, Pascal G., Nielsen, Aaraby Y., Terp, Mikkel G., Pedersen, Christina B., Guldberg, Per, Ditzel, Henrik J., Gjerstorff, Morten F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900521/
https://www.ncbi.nlm.nih.gov/pubmed/33634013
http://dx.doi.org/10.3389/fonc.2020.584024
_version_ 1783654223770025984
author Jakobsen, Mie K.
Traynor, Sofie
Stæhr, Mette
Duijf, Pascal G.
Nielsen, Aaraby Y.
Terp, Mikkel G.
Pedersen, Christina B.
Guldberg, Per
Ditzel, Henrik J.
Gjerstorff, Morten F.
author_facet Jakobsen, Mie K.
Traynor, Sofie
Stæhr, Mette
Duijf, Pascal G.
Nielsen, Aaraby Y.
Terp, Mikkel G.
Pedersen, Christina B.
Guldberg, Per
Ditzel, Henrik J.
Gjerstorff, Morten F.
author_sort Jakobsen, Mie K.
collection PubMed
description Identification of novel tumor-specific targets is important for the future development of immunotherapeutic strategies using genetically engineered T cells or vaccines. In this study, we characterized the expression of VCX2, a member of the VCX/Y cancer/testis antigen family, in a large panel of normal tissues and tumors from multiple cancer types using immunohistochemical staining and RNA expression data. In normal tissues, VCX2 was detected in the germ cells of the testis at all stages of maturation but not in any somatic tissues. Among malignancies, VCX2 was only found in tumors of a small subset of melanoma patients and thus rarely expressed compared to other cancer/testis antigens such as GAGE and MAGE-A. The expression of VCX2 correlated with that of other VCX/Y genes. Importantly, we found that expression of VCX2 was inversely correlated with promoter methylation and could be activated by treatment with a DNA methyltransferase inhibitor in multiple breast cancer and melanoma cell lines and a breast cancer patient-derived xenograft. The effect could be further potentiated by combining the DNA methyltransferase inhibitor with a histone deacetylase inhibitor. Our results show that the expression of VCX2 can be epigenetically induced in cancer cells and therefore could be an attractive target for immunotherapy of cancer.
format Online
Article
Text
id pubmed-7900521
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79005212021-02-24 The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors Jakobsen, Mie K. Traynor, Sofie Stæhr, Mette Duijf, Pascal G. Nielsen, Aaraby Y. Terp, Mikkel G. Pedersen, Christina B. Guldberg, Per Ditzel, Henrik J. Gjerstorff, Morten F. Front Oncol Oncology Identification of novel tumor-specific targets is important for the future development of immunotherapeutic strategies using genetically engineered T cells or vaccines. In this study, we characterized the expression of VCX2, a member of the VCX/Y cancer/testis antigen family, in a large panel of normal tissues and tumors from multiple cancer types using immunohistochemical staining and RNA expression data. In normal tissues, VCX2 was detected in the germ cells of the testis at all stages of maturation but not in any somatic tissues. Among malignancies, VCX2 was only found in tumors of a small subset of melanoma patients and thus rarely expressed compared to other cancer/testis antigens such as GAGE and MAGE-A. The expression of VCX2 correlated with that of other VCX/Y genes. Importantly, we found that expression of VCX2 was inversely correlated with promoter methylation and could be activated by treatment with a DNA methyltransferase inhibitor in multiple breast cancer and melanoma cell lines and a breast cancer patient-derived xenograft. The effect could be further potentiated by combining the DNA methyltransferase inhibitor with a histone deacetylase inhibitor. Our results show that the expression of VCX2 can be epigenetically induced in cancer cells and therefore could be an attractive target for immunotherapy of cancer. Frontiers Media S.A. 2021-02-09 /pmc/articles/PMC7900521/ /pubmed/33634013 http://dx.doi.org/10.3389/fonc.2020.584024 Text en Copyright © 2021 Jakobsen, Traynor, Stæhr, Duijf, Nielsen, Terp, Pedersen, Guldberg, Ditzel and Gjerstorff http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Jakobsen, Mie K.
Traynor, Sofie
Stæhr, Mette
Duijf, Pascal G.
Nielsen, Aaraby Y.
Terp, Mikkel G.
Pedersen, Christina B.
Guldberg, Per
Ditzel, Henrik J.
Gjerstorff, Morten F.
The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors
title The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors
title_full The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors
title_fullStr The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors
title_full_unstemmed The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors
title_short The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors
title_sort cancer/testis antigen gene vcx2 is rarely expressed in malignancies but can be epigenetically activated using dna methyltransferase and histone deacetylase inhibitors
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900521/
https://www.ncbi.nlm.nih.gov/pubmed/33634013
http://dx.doi.org/10.3389/fonc.2020.584024
work_keys_str_mv AT jakobsenmiek thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT traynorsofie thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT stæhrmette thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT duijfpascalg thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT nielsenaarabyy thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT terpmikkelg thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT pedersenchristinab thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT guldbergper thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT ditzelhenrikj thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT gjerstorffmortenf thecancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT jakobsenmiek cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT traynorsofie cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT stæhrmette cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT duijfpascalg cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT nielsenaarabyy cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT terpmikkelg cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT pedersenchristinab cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT guldbergper cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT ditzelhenrikj cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors
AT gjerstorffmortenf cancertestisantigengenevcx2israrelyexpressedinmalignanciesbutcanbeepigeneticallyactivatedusingdnamethyltransferaseandhistonedeacetylaseinhibitors