Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage

Detalhes bibliográficos
Autor(a) principal: Severino, P.F.
Data de Publicação: 2017
Outros Autores: Silva, M., Carrascal, M., Malagolini, N., Chiricolo, M., Venturi, G., Astolfi, A., Catera, M., Videira, P.A., Dall'Olio, F.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.18632/oncotarget.17138
Resumo: This work was supported by: Portuguese Foundation for Science and Technology (FCT) PhD grants SFRH/BD/45120/2008 (Paulo F. Severino), SFRH/BD/81860/2011 (Mariana Silva) and SFRH/BD/100970/2014 (Mylene Carrascal), Liga Portuguesa Contra o Cancro 2011 (Mylene A. Carrascal); Premio Inovacao Universidade de Coimbra and the Santander Totta/ Universidade NOVA de Lisboa prizes (Paula Videira). Grants from the University of Bologna (Fabio Dall'Olio). Mariangela Catera and Giulia Venturi are PhD students supported by grants from the University of Bologna.
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spelling Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damageBacillus Calmette-GuérinBladder cancerGlycosylationSialyl-Tn antigenST6GALNAC1 sialyltransferaseSDG 3 - Good Health and Well-beingThis work was supported by: Portuguese Foundation for Science and Technology (FCT) PhD grants SFRH/BD/45120/2008 (Paulo F. Severino), SFRH/BD/81860/2011 (Mariana Silva) and SFRH/BD/100970/2014 (Mylene Carrascal), Liga Portuguesa Contra o Cancro 2011 (Mylene A. Carrascal); Premio Inovacao Universidade de Coimbra and the Santander Totta/ Universidade NOVA de Lisboa prizes (Paula Videira). Grants from the University of Bologna (Fabio Dall'Olio). Mariangela Catera and Giulia Venturi are PhD students supported by grants from the University of Bologna.The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. Compared with MCRNc, BCGstimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. Consistently, MCRsTn cells displayed higher H2O2 sensitivity. In MCRsTn, BCG challenge induced an increased expression of several regulatory non coding RNA genes. These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. © Severino et al.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)DCV - Departamento de Ciências da VidaRUNSeverino, P.F.Silva, M.Carrascal, M.Malagolini, N.Chiricolo, M.Venturi, G.Astolfi, A.Catera, M.Videira, P.A.Dall'Olio, F.2017-10-13T22:01:54Z2017-082017-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12application/pdfhttps://doi.org/10.18632/oncotarget.17138eng1949-2553PURE: 3208988https://www.scopus.com/inward/record.uri?eid=2-s2.0-85029075729&doi=10.18632%2foncotarget.17138&partnerID=40&md5=0496578de8ac2a752d63075f123b7a4ehttps://doi.org/10.18632/oncotarget.17138info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:12:31Zoai:run.unl.pt:10362/24162Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:28:00.077270Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
title Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
spellingShingle Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
Severino, P.F.
Bacillus Calmette-Guérin
Bladder cancer
Glycosylation
Sialyl-Tn antigen
ST6GALNAC1 sialyltransferase
SDG 3 - Good Health and Well-being
title_short Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
title_full Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
title_fullStr Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
title_full_unstemmed Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
title_sort Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
author Severino, P.F.
author_facet Severino, P.F.
Silva, M.
Carrascal, M.
Malagolini, N.
Chiricolo, M.
Venturi, G.
Astolfi, A.
Catera, M.
Videira, P.A.
Dall'Olio, F.
author_role author
author2 Silva, M.
Carrascal, M.
Malagolini, N.
Chiricolo, M.
Venturi, G.
Astolfi, A.
Catera, M.
Videira, P.A.
Dall'Olio, F.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
DCV - Departamento de Ciências da Vida
RUN
dc.contributor.author.fl_str_mv Severino, P.F.
Silva, M.
Carrascal, M.
Malagolini, N.
Chiricolo, M.
Venturi, G.
Astolfi, A.
Catera, M.
Videira, P.A.
Dall'Olio, F.
dc.subject.por.fl_str_mv Bacillus Calmette-Guérin
Bladder cancer
Glycosylation
Sialyl-Tn antigen
ST6GALNAC1 sialyltransferase
SDG 3 - Good Health and Well-being
topic Bacillus Calmette-Guérin
Bladder cancer
Glycosylation
Sialyl-Tn antigen
ST6GALNAC1 sialyltransferase
SDG 3 - Good Health and Well-being
description This work was supported by: Portuguese Foundation for Science and Technology (FCT) PhD grants SFRH/BD/45120/2008 (Paulo F. Severino), SFRH/BD/81860/2011 (Mariana Silva) and SFRH/BD/100970/2014 (Mylene Carrascal), Liga Portuguesa Contra o Cancro 2011 (Mylene A. Carrascal); Premio Inovacao Universidade de Coimbra and the Santander Totta/ Universidade NOVA de Lisboa prizes (Paula Videira). Grants from the University of Bologna (Fabio Dall'Olio). Mariangela Catera and Giulia Venturi are PhD students supported by grants from the University of Bologna.
publishDate 2017
dc.date.none.fl_str_mv 2017-10-13T22:01:54Z
2017-08
2017-08-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.18632/oncotarget.17138
url https://doi.org/10.18632/oncotarget.17138
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1949-2553
PURE: 3208988
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85029075729&doi=10.18632%2foncotarget.17138&partnerID=40&md5=0496578de8ac2a752d63075f123b7a4e
https://doi.org/10.18632/oncotarget.17138
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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