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

Bassagañas, Sònia; Allende, Helena; Cobler Moncunill, Lara, 1985-; Ortiz, María Rosa; Llop Escorihuela, Esther; Bolos Pi, Ma. Carmen de; Peracaula, Rosa

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

Mostra el registre complet Registre parcial de l'ítem

dc.contributor.author Bassagañas, Sòniaca
dc.contributor.author Allende, Helenaca
dc.contributor.author Cobler Moncunill, Lara, 1985-ca
dc.contributor.author Ortiz, María Rosaca
dc.contributor.author Llop Escorihuela, Estherca
dc.contributor.author Bolos Pi, Ma. Carmen deca
dc.contributor.author Peracaula, Rosaca
dc.date.accessioned 2015-09-03T09:38:49Z
dc.date.available 2016-09-30T02:00:05Z
dc.date.issued 2015
dc.description.abstract 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 sialyl-Lewis(x) (SLe(x)) 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-1β, TNFα, 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 mmunohistochemistry to find a possible correlation between inflammation status and the presence of tumor-associated carbohydrate antigens. RESULTS: IL-1β stimuli increased SLe(x) and α2,6-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 SLe(x) biosynthesis, and of ST6GAL1. IL-6 and TNFα treatments increased the levels of SLe(x) and Le(y) 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 SLe(x) and SLe(a) 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 SLe(x), which contributes to pancreatic tumor malignancy.ca
dc.description.sponsorship This 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 fellowship.
dc.format.mimetype application/pdfca
dc.identifier.citation Bassagañas S, Allende H, Cobler L, Ortiz MR, Llop E, de Bolós C. et al. Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines. Cytokine. 2015 Sep;75(1):197-206. doi: 10.1016/j.cyto.2015.04.006ca
dc.identifier.doi http://dx.doi.org/10.1016/j.cyto.2015.04.006
dc.identifier.issn 1043-4666
dc.identifier.uri http://hdl.handle.net/10230/24728
dc.language.iso engca
dc.publisher Elsevierca
dc.relation.ispartof Cytokine. 2015 Sep;75(1):197-206
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2010-16922
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Pàncrees -- Tumorsca
dc.subject.other Càncerca
dc.title Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

Col·leccions

Articles (Hospital del Mar Research Institute)