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The Glycan CA19-9 Promotes Pancreatitis and Pancreatic Cancer in Mice

The Glycan CA19-9 Promotes Pancreatitis and Pancreatic Cancer in Mice

Dannielle D Engle, Hervé Tiriac, Keith D Rivera, Arnaud Pommier, Sean Whalen, Tobiloba E Oni, Brinda Alagesan, Eun Jung Lee, Melissa A Yao, Matthew S Lucito, Benjamin Spielman, Brandon Da Silva, Christina Schoepfer, etc.

Science. 2019 Jun 21;364(6446):1156-1162.

PMID: 31221853

Abstract:

Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these alterations contribute to disease pathogenesis is largely unknown. To study the role of glycan changes in pancreatic disease, we inducibly expressed human fucosyltransferase 3 and β1,3-galactosyltransferase 5 in mice, reconstituting the glycan sialyl-Lewisa, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19-9 modification of the matricellular protein fibulin-3 increased its interaction with EGFR, and blockade of fibulin-3, EGFR ligands, or CA19-9 prevented EGFR hyperactivation in organoids. CA19-9-mediated pancreatitis was reversible and could be suppressed with CA19-9 antibodies. CA19-9 also cooperated with the KrasG12D oncogene to produce aggressive pancreatic cancer. These findings implicate CA19-9 in the etiology of pancreatitis and pancreatic cancer and nominate CA19-9 as a therapeutic target.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP959417857	9,9-Dioctyl-9H-fluoren-2-amine		959417-85-7	Price

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