Title

Mucin glycosylation is altered by pro-inflammatory signaling in pancreatic-cancer cells

Document Type

Article

Publication Date

4-2009

Keywords

mucin, glycosylation, pro-inflammatory cytokines, antibody array, pancreatic cancer

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. Using a novel antibody-glycan microarray method, we measured the effects of pro-inflammatory stimuli (oxidative stress and treatment with the cytokines IFNγ, IL-1α, and TNFα) 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 β1,4-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.

Journal Title

Journal of Proteome Research

Volume

8

Issue

4

First Page

1876

Last Page

1886

DOI

10.1021/pr8008379

First Department

Chemistry and Biochemistry

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