title: Regulation of glycosyltransferases and Lewis antigens expression by IL-1β and IL-6 in human gastric cancer cells.
abstract: Inflammation of stomach mucosa has been postulated as initiator of gastric carcinogenesis and the presence of pro-inflammatory cytokines can regulate specific genes involved in this process. The cellular expression pattern of glycosyltransferases and Lewis antigens detected in the normal mucosa changed during the neoplassic transformation. The aim of this work was to determine the regulation of specific fucosyltransferases and sialyltransferases by IL-1β and IL-6 pro-inflammatory cytokines in MKN45 gastric cancer cells. IL-1β induced significant increases in the mRNA levels of FUT1, FUT2 and FUT4, and decreases of FUT3 and FUT5. In IL-6 treatments, enhanced FUT1 and lower FUT3 and FUT5 mRNA expression were detected. No substantial changes were observed in the levels of ST3GalIII and ST3GalIV. The activation of FUT1, FUT2 and FUT4 by IL-1β is through the NF-κB pathway and the down-regulation of FUT3 and FUT5 by IL-6 is through the gp130/STAT-3 pathway, since they are inhibited specifically by panepoxydone and AG490, respectively. The levels of Lewis antigens after IL-1β or IL-6 stimulation decreased for sialyl-Lewis x, and no significant differences were found in the rest of the Lewis antigens analyzed, as it was also observed in subcutaneous mice tumors from MKN45 cells treated with IL-1β or IL-6. In addition, in 61 human intestinal-type gastric tumors, sialyl-Lewis x was highly detected in samples from patients that developed metastasis. These results indicate that the expression of the fucosyltransferases involved in the synthesis of Lewis antigens in gastric cancer cells can be specifically modulated by IL-1β and IL-6 inflammatory cytokines.
authors.affiliation: Programa de Recerca en Càncer, IMIM-Hospital del Mar, 08003 Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Padró
authors.forename: Raquel
authors.initials: R
authors.lastname: Mejías-Luque
authors.forename: Lara
authors.initials: L
authors.lastname: Cobler
authors.forename: Marta
authors.initials: M
authors.lastname: Garrido
authors.forename: Marta
authors.initials: M
authors.lastname: Pérez-Garay
authors.forename: Sònia
authors.initials: S
authors.lastname: Puig
authors.forename: Rosa
authors.initials: R
authors.lastname: Peracaula
authors.forename: Carme
authors.initials: C
authors.lastname: de Bolós
mesh_terms: D000818:Animals; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007983:Lewis Blood Group Antigens / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009844:Oligosaccharides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D000080506:Sialyl Lewis X Antigen; D050822:Cytokine Receptor gp130; D016695:Glycosyltransferases