Aberrant Glycosylation Promotes Pancreatic Inflammation

CA19-9 is a glycan elevated in human gastrointestinal pathologies, but absent from rodents. We humanized the mouse glycome and found that CA19-9 is not only a correlative biomarker of pancreatic disease, but also plays a causative role in the initiation of pancreatitis. Elevation of CA19-9 results in the activation of EGFR signaling in the normal pancreatic ductal compartment through secretion of Fibulin 3. These signaling changes can be blocked by blocking either CA19-9 or Fibulin 3.