Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma containing several pro-inflammatory cytokines, which are described to modulate the expression of important genes related to tumor promotion and progression. In the present work we have investigated the potenti...

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Autores: Bassagañas i Puigdemont, Sònia, Allende, Helena, Cobler, Lara, Ortiz Duran, Maria Rosa, Llop Escorihuela, Esther, Bolòs, Carme de, Peracaula Miró, Rosa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/11634
Acceso en línea:http://hdl.handle.net/10256/11634
Access Level:acceso embargado
Palabra clave:Citocines
Cytokines
Pàncrees -- Càncer
Pancreas -- Cancer
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spelling Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell linesBassagañas i Puigdemont, SòniaAllende, HelenaCobler, LaraOrtiz Duran, Maria RosaLlop Escorihuela, EstherBolòs, Carme dePeracaula Miró, RosaCitocinesCytokinesPàncrees -- CàncerPancreas -- CancerBackground: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma containing several pro-inflammatory cytokines, which are described to modulate the expression of important genes related to tumor promotion and progression. In the present work we have investigated the potential role of these cytokines in the biosynthesis of tumor-associated carbohydrate antigens such as sialylLewisx (SLex) through the regulation of specific glycosyltransferase genes. Methods: Two human PDAC cell lines MDAPanc-3 and MDAPanc-28 were treated with pro-inflammatory cytokines IL-1b, TNFa, IL-6 or IL-8, and the content of tumor-associated carbohydrate antigens at the cell membrane was analyzed by flow cytometry. In addition, variation in the mRNA expression of sialyltransferase (ST) and fucosyltransferase (FUT) genes, which codify for the ST and FucT enzymes involved in the carbohydrate antigens’ biosynthesis, was determined. The inflammatory microenvironment of PDAC tissues and the expression of Lewis-type antigens were analyzed by immunohistochemistry to find a possible correlation between inflammation status and the presence of tumor-associated carbohydrate antigens. Results: IL-1b stimuli increased SLex and a2,6-sialic acid levels in MDAPanc-28 cells and enhanced the mRNA levels of ST3GAL3-4 and FUT5-7, which codify for ST and FucT enzymes related to SLex biosynthesis, and of ST6GAL1. IL-6 and TNFa treatments increased the levels of SLex and Ley antigens in MDPanc-3 cells and, similarly, the mRNA expression of ST3GAL3-4, FUT1-2 and FUT6, related to these Lewis-type antigens’ biosynthesis, were increased. Most PDAC tissues stained for SLex and SLea and tended to be expressed in the tumor samples with a higher presence of inflammatory immune cells. Conclusions: The inflammatory microenvironment can modulate the glycosylation pattern of PDAC cells, increasing the expression of tumor-associated sialylated antigens such as SLex , which contributes to pancreatic tumor malignancyThis work was supported by the Spanish Ministerio de Ciencia e Innovación (Grant BIO2010-16922, awarded to RP) and by the Fundació La Marató de TV3 (Grant 050932, awarded to RP). SB acknowledges the Government of Catalonia for a pre-doctoral fellowshipElsevierMinisterio de Ciencia e Innovación (Espanya)infoinfo2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10256/11634http://hdl.handle.net/10256/11634© Cytokine, 2015, vol. 75, p. 197-206Articles publicats (D-B)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.cyto.2015.04.006info:eu-repo/semantics/altIdentifier/issn/1043-4666info:eu-repo/grantAgreement/MICINN//BIO2010-16922Tots els drets reservatsinfo:eu-repo/semantics/embargoedAccessoai:recercat.cat:10256/116342026-05-29T05:05:01Z
dc.title.none.fl_str_mv Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
title Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
spellingShingle Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
Bassagañas i Puigdemont, Sònia
Citocines
Cytokines
Pàncrees -- Càncer
Pancreas -- Cancer
title_short Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
title_full Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
title_fullStr Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
title_full_unstemmed Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
title_sort Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines
dc.creator.none.fl_str_mv Bassagañas i Puigdemont, Sònia
Allende, Helena
Cobler, Lara
Ortiz Duran, Maria Rosa
Llop Escorihuela, Esther
Bolòs, Carme de
Peracaula Miró, Rosa
author Bassagañas i Puigdemont, Sònia
author_facet Bassagañas i Puigdemont, Sònia
Allende, Helena
Cobler, Lara
Ortiz Duran, Maria Rosa
Llop Escorihuela, Esther
Bolòs, Carme de
Peracaula Miró, Rosa
author_role author
author2 Allende, Helena
Cobler, Lara
Ortiz Duran, Maria Rosa
Llop Escorihuela, Esther
Bolòs, Carme de
Peracaula Miró, Rosa
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (Espanya)
dc.subject.none.fl_str_mv Citocines
Cytokines
Pàncrees -- Càncer
Pancreas -- Cancer
topic Citocines
Cytokines
Pàncrees -- Càncer
Pancreas -- Cancer
description Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma containing several pro-inflammatory cytokines, which are described to modulate the expression of important genes related to tumor promotion and progression. In the present work we have investigated the potential role of these cytokines in the biosynthesis of tumor-associated carbohydrate antigens such as sialylLewisx (SLex) through the regulation of specific glycosyltransferase genes. Methods: Two human PDAC cell lines MDAPanc-3 and MDAPanc-28 were treated with pro-inflammatory cytokines IL-1b, TNFa, IL-6 or IL-8, and the content of tumor-associated carbohydrate antigens at the cell membrane was analyzed by flow cytometry. In addition, variation in the mRNA expression of sialyltransferase (ST) and fucosyltransferase (FUT) genes, which codify for the ST and FucT enzymes involved in the carbohydrate antigens’ biosynthesis, was determined. The inflammatory microenvironment of PDAC tissues and the expression of Lewis-type antigens were analyzed by immunohistochemistry to find a possible correlation between inflammation status and the presence of tumor-associated carbohydrate antigens. Results: IL-1b stimuli increased SLex and a2,6-sialic acid levels in MDAPanc-28 cells and enhanced the mRNA levels of ST3GAL3-4 and FUT5-7, which codify for ST and FucT enzymes related to SLex biosynthesis, and of ST6GAL1. IL-6 and TNFa treatments increased the levels of SLex and Ley antigens in MDPanc-3 cells and, similarly, the mRNA expression of ST3GAL3-4, FUT1-2 and FUT6, related to these Lewis-type antigens’ biosynthesis, were increased. Most PDAC tissues stained for SLex and SLea and tended to be expressed in the tumor samples with a higher presence of inflammatory immune cells. Conclusions: The inflammatory microenvironment can modulate the glycosylation pattern of PDAC cells, increasing the expression of tumor-associated sialylated antigens such as SLex , which contributes to pancreatic tumor malignancy
publishDate 2015
dc.date.none.fl_str_mv 2015
info
info
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/11634
http://hdl.handle.net/10256/11634
url http://hdl.handle.net/10256/11634
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cyto.2015.04.006
info:eu-repo/semantics/altIdentifier/issn/1043-4666
info:eu-repo/grantAgreement/MICINN//BIO2010-16922
dc.rights.none.fl_str_mv Tots els drets reservats
info:eu-repo/semantics/embargoedAccess
rights_invalid_str_mv Tots els drets reservats
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv © Cytokine, 2015, vol. 75, p. 197-206
Articles publicats (D-B)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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repository.mail.fl_str_mv
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