Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/45057 |
Resumo: | Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. |
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Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressivenessChemoresistanceMonocarboxylate transportersMetabolic compartmentsTumour stromaUrothelial bladder cancertumor stromaScience & TechnologyMonocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance.This study was supported by the Life and Health Sciences Research Institute (ICVS) from the School of Health Sciences of the University of Minho. JA received a postdoctoral fellowship from ICVS (reference ICVS-SSRL: ON.2 SR&TD Integrated Program, NORTE-07-0124-FEDER-000017).info:eu-repo/semantics/publishedVersionTaylor and FrancisUniversidade do MinhoAfonso, Julieta Alexandra PereiraSantos, Lúcio L.Morais, A.Amaro, TeresinaLongatto Filho, AdhemarBaltazar, Maria de Fátima Monginho2016-122016-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/45057engAfonso, J., Santos, L. L., Morais, A., Amaro, T., Longatto-Filho, A., & Baltazar, F. (2016). Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness. Cell Cycle, 15(3), 368-380. doi: 10.1080/15384101.2015.11213291538-41011551-400510.1080/15384101.2015.112132926636903http://www.tandfonline.com/doi/full/10.1080/15384101.2015.1121329#.VnFyoDalw68info: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:RCAAP2023-07-21T12:52:54Zoai:repositorium.sdum.uminho.pt:1822/45057Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:52:08.721832Repositório 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 |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness |
title |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness |
spellingShingle |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness Afonso, Julieta Alexandra Pereira Chemoresistance Monocarboxylate transporters Metabolic compartments Tumour stroma Urothelial bladder cancer tumor stroma Science & Technology |
title_short |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness |
title_full |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness |
title_fullStr |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness |
title_full_unstemmed |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness |
title_sort |
Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness |
author |
Afonso, Julieta Alexandra Pereira |
author_facet |
Afonso, Julieta Alexandra Pereira Santos, Lúcio L. Morais, A. Amaro, Teresina Longatto Filho, Adhemar Baltazar, Maria de Fátima Monginho |
author_role |
author |
author2 |
Santos, Lúcio L. Morais, A. Amaro, Teresina Longatto Filho, Adhemar Baltazar, Maria de Fátima Monginho |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Afonso, Julieta Alexandra Pereira Santos, Lúcio L. Morais, A. Amaro, Teresina Longatto Filho, Adhemar Baltazar, Maria de Fátima Monginho |
dc.subject.por.fl_str_mv |
Chemoresistance Monocarboxylate transporters Metabolic compartments Tumour stroma Urothelial bladder cancer tumor stroma Science & Technology |
topic |
Chemoresistance Monocarboxylate transporters Metabolic compartments Tumour stroma Urothelial bladder cancer tumor stroma Science & Technology |
description |
Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12 2016-12-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/45057 |
url |
http://hdl.handle.net/1822/45057 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Afonso, J., Santos, L. L., Morais, A., Amaro, T., Longatto-Filho, A., & Baltazar, F. (2016). Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness. Cell Cycle, 15(3), 368-380. doi: 10.1080/15384101.2015.1121329 1538-4101 1551-4005 10.1080/15384101.2015.1121329 26636903 http://www.tandfonline.com/doi/full/10.1080/15384101.2015.1121329#.VnFyoDalw68 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Taylor and Francis |
publisher.none.fl_str_mv |
Taylor and Francis |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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