Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage
| Autor(a) principal: | |
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| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , |
| 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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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:RCAAP2023-07-10T15:40:40ZPortal AgregadorONG |
| 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 |
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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 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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12 application/pdf |
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