Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer

Summary: Stem cells are emerging sources of antigens for cancer immunotherapy. Here, we used TNG-A mouse embryonic stem cells to trigger an anticancer response against tumors derived from E0771 mouse breast cancer cells, possibly mediated by the mouse immune system. TNG-A cells were cultured in the...

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Main Authors: Magda Correia, Carlota Tavares-Marcos, João Pessoa, Miguel Casanova, Bruno Cavadas, Rui Vitorino, Júlia Tavares e Silva, Francisca Mateus, Guadalupe Espadas, Mariana Pinheiro, Catarina Alves-Vale, Eduard Sabidó, Bruno Neves, Sandrina Nóbrega-Pereira, Bruno Bernardes de Jesus
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225009496
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author Magda Correia
Carlota Tavares-Marcos
João Pessoa
Miguel Casanova
Bruno Cavadas
Rui Vitorino
Júlia Tavares e Silva
Francisca Mateus
Guadalupe Espadas
Mariana Pinheiro
Catarina Alves-Vale
Eduard Sabidó
Bruno Neves
Sandrina Nóbrega-Pereira
Bruno Bernardes de Jesus
author_facet Magda Correia
Carlota Tavares-Marcos
João Pessoa
Miguel Casanova
Bruno Cavadas
Rui Vitorino
Júlia Tavares e Silva
Francisca Mateus
Guadalupe Espadas
Mariana Pinheiro
Catarina Alves-Vale
Eduard Sabidó
Bruno Neves
Sandrina Nóbrega-Pereira
Bruno Bernardes de Jesus
author_sort Magda Correia
collection DOAJ
description Summary: Stem cells are emerging sources of antigens for cancer immunotherapy. Here, we used TNG-A mouse embryonic stem cells to trigger an anticancer response against tumors derived from E0771 mouse breast cancer cells, possibly mediated by the mouse immune system. TNG-A cells were cultured in the presence or absence of two specific kinase inhibitors. While the inhibitors preserved TNG-A pluripotency, their removal altered the morphology, transcriptome, and proteome of TNG-A cells, increasing their similarities with E0771 cancer cells. Double pre-exposure by subcutaneous injection of TNG-A cells followed by E0771 implantation drastically decreased E0771-derived tumor size in mice. Serum cytokine quantifications suggested a transient immune reaction associated with tumor regression. Nevertheless, pre-exposure to TNG-A cells impaired for the tight junction protein Claudin 6 failed to decrease tumor size. Our findings demonstrate the anti-tumor effects of embryonic stem cells and anticipate their potential as an allogenic source for cancer immunotherapy.
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publisher Elsevier
record_format Article
series iScience
spelling doaj-art-3c2c585fecce44b4b5ced1eee4e7cc7b2025-08-20T02:17:19ZengElsevieriScience2589-00422025-06-0128611268810.1016/j.isci.2025.112688Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancerMagda Correia0Carlota Tavares-Marcos1João Pessoa2Miguel Casanova3Bruno Cavadas4Rui Vitorino5Júlia Tavares e Silva6Francisca Mateus7Guadalupe Espadas8Mariana Pinheiro9Catarina Alves-Vale10Eduard Sabidó11Bruno Neves12Sandrina Nóbrega-Pereira13Bruno Bernardes de Jesus14Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalCenter for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain; Universitat Pompeu Fabra, 08002 Barcelona, SpainDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; Hospital CUF Descobertas, CUF Oncologia, 1998-018 Lisbon, PortugalCenter for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain; Universitat Pompeu Fabra, 08002 Barcelona, SpainDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; Corresponding authorDepartment of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; Corresponding authorSummary: Stem cells are emerging sources of antigens for cancer immunotherapy. Here, we used TNG-A mouse embryonic stem cells to trigger an anticancer response against tumors derived from E0771 mouse breast cancer cells, possibly mediated by the mouse immune system. TNG-A cells were cultured in the presence or absence of two specific kinase inhibitors. While the inhibitors preserved TNG-A pluripotency, their removal altered the morphology, transcriptome, and proteome of TNG-A cells, increasing their similarities with E0771 cancer cells. Double pre-exposure by subcutaneous injection of TNG-A cells followed by E0771 implantation drastically decreased E0771-derived tumor size in mice. Serum cytokine quantifications suggested a transient immune reaction associated with tumor regression. Nevertheless, pre-exposure to TNG-A cells impaired for the tight junction protein Claudin 6 failed to decrease tumor size. Our findings demonstrate the anti-tumor effects of embryonic stem cells and anticipate their potential as an allogenic source for cancer immunotherapy.http://www.sciencedirect.com/science/article/pii/S2589004225009496CancerStem cells research
spellingShingle Magda Correia
Carlota Tavares-Marcos
João Pessoa
Miguel Casanova
Bruno Cavadas
Rui Vitorino
Júlia Tavares e Silva
Francisca Mateus
Guadalupe Espadas
Mariana Pinheiro
Catarina Alves-Vale
Eduard Sabidó
Bruno Neves
Sandrina Nóbrega-Pereira
Bruno Bernardes de Jesus
Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer
iScience
Cancer
Stem cells research
title Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer
title_full Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer
title_fullStr Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer
title_full_unstemmed Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer
title_short Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer
title_sort claudin 6 mediates an embryonic stem cell driven antitumor response against breast cancer
topic Cancer
Stem cells research
url http://www.sciencedirect.com/science/article/pii/S2589004225009496
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