The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer

Festari, María Florencia - da Costa, Valeria - Rodríguez-Zraquia, Santiago A. - Costa, Monique - Landeira, Mercedes - Lores, Pablo - Solari-Saquieres, Patricia - Kramer, M. Gabriela - Freire, Teresa

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.


Detalles Bibliográficos
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
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/39751
https://doi.org/10.1093/glycob/cwab123
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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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
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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
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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
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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