The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer
Resumen:
Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.
2021 | |
Immunoregulation Metastasis Tn antigen Triple negative breast cancer Tumor growth LUNG NEOPLASM TRIPLE NEGATIVE BREAST NEOPLASMS METABOLISM PATHOLOGY ANTIGENS CELL LINE ANTIGENOS LINEA CELULAR NEOPLASIAS PULMONARES METABOLISMO PATOLOGIA NEOPLASIAS DE LA MAMA TRIPLE NEGATIVAS |
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Inglés | |
Universidad de la República | |
COLIBRI | |
https://hdl.handle.net/20.500.12008/39751
https://doi.org/10.1093/glycob/cwab123 |
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Acceso abierto | |
Licencia Creative Commons Atribución (CC - By 4.0) |
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author | Festari, María Florencia |
author2 | da Costa, Valeria Rodríguez-Zraquia, Santiago A. Costa, Monique Landeira, Mercedes Lores, Pablo Solari-Saquieres, Patricia Kramer, M. Gabriela Freire, Teresa |
author2_role | author author author author author author author author |
author_facet | Festari, María Florencia da Costa, Valeria Rodríguez-Zraquia, Santiago A. Costa, Monique Landeira, Mercedes Lores, Pablo Solari-Saquieres, Patricia Kramer, M. Gabriela Freire, Teresa |
author_role | author |
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collection | COLIBRI |
dc.contributor.filiacion.none.fl_str_mv | Festari María Florencia, Universidad de la República (Uruguay). Facultad de Medicina da Costa Valeria, Universidad de la República (Uruguay). Facultad de Medicina Rodríguez-Zraquia Santiago A., Universidad de la República (Uruguay). Facultad de Medicina Costa Monique, Universidad de la República (Uruguay). Facultad de Medicina Landeira Mercedes, Universidad de la República (Uruguay). Facultad de Medicina Lores Pablo, Universidad de la República (Uruguay). Facultad de Medicina Solari-Saquieres Patricia, Universidad de la República (Uruguay). Facultad de Medicina Kramer M. Gabriela, Universidad de la República (Uruguay). Facultad de Medicina Freire Teresa, Universidad de la República (Uruguay). Facultad de Medicina |
dc.creator.none.fl_str_mv | Festari, María Florencia da Costa, Valeria Rodríguez-Zraquia, Santiago A. Costa, Monique Landeira, Mercedes Lores, Pablo Solari-Saquieres, Patricia Kramer, M. Gabriela Freire, Teresa |
dc.date.accessioned.none.fl_str_mv | 2023-08-31T16:11:10Z |
dc.date.available.none.fl_str_mv | 2023-08-31T16:11:10Z |
dc.date.issued.none.fl_str_mv | 2021 |
dc.description.abstract.none.fl_txt_mv | Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors. |
dc.description.es.fl_txt_mv | Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay -- Contacto: tfreire@fmed.edu.uy |
dc.format.extent.es.fl_str_mv | 14 p. |
dc.format.mimetype.es.fl_str_mv | application/pdf |
dc.identifier.citation.es.fl_str_mv | Festari F, da Costa V, Rodríguez-Zraquia S y otros. The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer. Glycobiology [en línea] 2022, 32(5): 366–379 |
dc.identifier.doi.none.fl_str_mv | https://doi.org/10.1093/glycob/cwab123 |
dc.identifier.issn.none.fl_str_mv | 0959-6658 |
dc.identifier.uri.none.fl_str_mv | https://hdl.handle.net/20.500.12008/39751 |
dc.language.iso.none.fl_str_mv | en eng |
dc.publisher.es.fl_str_mv | Oxford University Press |
dc.relation.ispartof.es.fl_str_mv | Glycobiology, 2022, 32(5): 366–379 |
dc.rights.license.none.fl_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess |
dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
dc.subject.es.fl_str_mv | Immunoregulation Metastasis Tn antigen Triple negative breast cancer Tumor growth |
dc.subject.other.es.fl_str_mv | LUNG NEOPLASM TRIPLE NEGATIVE BREAST NEOPLASMS METABOLISM PATHOLOGY ANTIGENS CELL LINE ANTIGENOS LINEA CELULAR NEOPLASIAS PULMONARES METABOLISMO PATOLOGIA NEOPLASIAS DE LA MAMA TRIPLE NEGATIVAS |
dc.title.none.fl_str_mv | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer |
dc.type.es.fl_str_mv | Artículo |
dc.type.none.fl_str_mv | info:eu-repo/semantics/article |
dc.type.version.none.fl_str_mv | info:eu-repo/semantics/publishedVersion |
description | Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay -- Contacto: tfreire@fmed.edu.uy |
eu_rights_str_mv | openAccess |
format | article |
id | COLIBRI_ead20e91ff82d1c9c79a08a8f635e86d |
identifier_str_mv | Festari F, da Costa V, Rodríguez-Zraquia S y otros. The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer. Glycobiology [en línea] 2022, 32(5): 366–379 0959-6658 |
instacron_str | Universidad de la República |
institution | Universidad de la República |
instname_str | Universidad de la República |
language | eng |
language_invalid_str_mv | en |
network_acronym_str | COLIBRI |
network_name_str | COLIBRI |
oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/39751 |
publishDate | 2021 |
reponame_str | COLIBRI |
repository.mail.fl_str_mv | mabel.seroubian@seciu.edu.uy |
repository.name.fl_str_mv | COLIBRI - Universidad de la República |
repository_id_str | 4771 |
rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
spelling | Festari María Florencia, Universidad de la República (Uruguay). Facultad de Medicinada Costa Valeria, Universidad de la República (Uruguay). Facultad de MedicinaRodríguez-Zraquia Santiago A., Universidad de la República (Uruguay). Facultad de MedicinaCosta Monique, Universidad de la República (Uruguay). Facultad de MedicinaLandeira Mercedes, Universidad de la República (Uruguay). Facultad de MedicinaLores Pablo, Universidad de la República (Uruguay). Facultad de MedicinaSolari-Saquieres Patricia, Universidad de la República (Uruguay). Facultad de MedicinaKramer M. Gabriela, Universidad de la República (Uruguay). Facultad de MedicinaFreire Teresa, Universidad de la República (Uruguay). Facultad de Medicina2023-08-31T16:11:10Z2023-08-31T16:11:10Z2021Festari F, da Costa V, Rodríguez-Zraquia S y otros. The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer. Glycobiology [en línea] 2022, 32(5): 366–3790959-6658https://hdl.handle.net/20.500.12008/39751https://doi.org/10.1093/glycob/cwab123Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay -- Contacto: tfreire@fmed.edu.uyCancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.Submitted by Almiñana María Cecilia (marialminana@gmail.com) on 2023-08-30T15:59:16Z No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) FestariFetall.pdf: 1720661 bytes, checksum: 22bf6b5e5229d8ed1154c983c10db228 (MD5)Approved for entry into archive by Almiñana María Cecilia (marialminana@gmail.com) on 2023-08-31T15:27:37Z (GMT) No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) FestariFetall.pdf: 1720661 bytes, checksum: 22bf6b5e5229d8ed1154c983c10db228 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2023-08-31T16:11:10Z (GMT). No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) FestariFetall.pdf: 1720661 bytes, checksum: 22bf6b5e5229d8ed1154c983c10db228 (MD5) Previous issue date: 202114 p.application/pdfenengOxford University PressGlycobiology, 2022, 32(5): 366–379Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)ImmunoregulationMetastasisTn antigenTriple negative breast cancerTumor growthLUNG NEOPLASMTRIPLE NEGATIVE BREAST NEOPLASMSMETABOLISMPATHOLOGYANTIGENSCELL LINEANTIGENOSLINEA CELULARNEOPLASIAS PULMONARESMETABOLISMOPATOLOGIANEOPLASIAS DE LA MAMA TRIPLE NEGATIVASThe tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancerArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaFestari, María Florenciada Costa, ValeriaRodríguez-Zraquia, Santiago A.Costa, MoniqueLandeira, MercedesLores, PabloSolari-Saquieres, PatriciaKramer, M. 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- Universidad de la Repúblicafalse |
spellingShingle | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer Festari, María Florencia Immunoregulation Metastasis Tn antigen Triple negative breast cancer Tumor growth LUNG NEOPLASM TRIPLE NEGATIVE BREAST NEOPLASMS METABOLISM PATHOLOGY ANTIGENS CELL LINE ANTIGENOS LINEA CELULAR NEOPLASIAS PULMONARES METABOLISMO PATOLOGIA NEOPLASIAS DE LA MAMA TRIPLE NEGATIVAS |
status_str | publishedVersion |
title | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer |
title_full | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer |
title_fullStr | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer |
title_full_unstemmed | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer |
title_short | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer |
title_sort | The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer |
topic | Immunoregulation Metastasis Tn antigen Triple negative breast cancer Tumor growth LUNG NEOPLASM TRIPLE NEGATIVE BREAST NEOPLASMS METABOLISM PATHOLOGY ANTIGENS CELL LINE ANTIGENOS LINEA CELULAR NEOPLASIAS PULMONARES METABOLISMO PATOLOGIA NEOPLASIAS DE LA MAMA TRIPLE NEGATIVAS |
url | https://hdl.handle.net/20.500.12008/39751 https://doi.org/10.1093/glycob/cwab123 |