title: Mucin glycosylation is altered by pro-inflammatory signaling in pancreatic-cancer cells.
abstract: Altered glycosylation on the surfaces or secreted proteins of tumor cells is common in pancreatic cancer and is thought to promote cancer progression, but the factors leading to the changes in carbohydrate structures are incompletely understood. We hypothesized that pro-inflammatory conditions can lead to alterations in cancer-associated glycans on mucins produced by pancreatic-cancer cells. With the use of a novel antibody-glycan microarray method, we measured the effects of pro-inflammatory stimuli (oxidative stress and treatment with the cytokines IFNgamma, IL-1alpha, and TNFalpha) on the expression and glycosylation of the mucins MUC1, MUC5AC, and MUC16 in multiple pancreatic cancer cell lines. Mucin glycosylation was significantly affected in specific cell lines, particularly in structures involving terminal galactose or N-acetylgalactosamine. In addition, the responses of the cell lines grouped according to the expression of cell-surface markers that are associated with tumorigenicity, as cell lines bearing minimal surface markers, showed evidence of increased O-glycan extension and decreased presentation of terminal beta1,4-linked galactose, opposite to cell lines bearing multiple markers. These results suggest mechanisms whereby inflammation might influence tumor behavior in a cell-type specific manner through modulating the presentation of cancer-associated glycans.
authors.affiliation: Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
authors.forename: Yi-Mi
authors.initials: YM
authors.lastname: Wu
authors.forename: D David
authors.initials: DD
authors.lastname: Nowack
authors.forename: Gilbert S
authors.initials: GS
authors.lastname: Omenn
authors.forename: Brian B
authors.initials: BB
authors.lastname: Haab
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D009077:Mucins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D009077:Mucins