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

Text Complet
Inflammatory-cytokines-regulate.pdf closed access
Sol·licita còpia a l'autor de l'article
En omplir aquest formulari esteu demanant una còpia de l'article dipositat al repositori institucional (DUGiDocs) al seu autor o a l'autor principal de l'article. Serà el mateix autor qui decideixi lliurar una còpia del document a qui ho sol•liciti si ho creu convenient. En tot cas, la Biblioteca de la UdG no intervé en aquest procés ja que no està autoritzada a facilitar articles quan aquests són d'accés restringit.
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 ​
​Tots els drets reservats