Sweet but nasty
Pancreatitis is an inflammation of the pancreas, which causes 275,000 hospitalizations annually in the United States. Patients suffering from hereditary pancreatitis have a lifetime risk of developing pancreatic cancer from 40 to 50 percent.
Dannielle Engle, a former researcher at the Cold Spring Harbor Cancer Laboratory (CSHL), recently appointed associate professor at the Salk Institute, studies the transformation of pancreatitis into pancreatic cancer. She identified a potentially powerful biomarker – a chemical structure called CA19-9, because its level is always elevated in patients with pancreatitis and pancreatic cancer. Now Engle and her research team have provided the first evidence that CA19-9 actually causes the disease with which it correlated as a biomarker, and suggest that blocking this polysaccharide will help prevent the progression of pancreatitis into pancreatic cancer.
Engle investigated the properties of pancreatic cancer cells. She focused on carbohydrate antigen 19-9 (carbohydrate antigen 19-9, CA19-9), a tetrasaccharide that covers many proteins but does not perform any specific function. In humans, the final stage of CA19-9 production is controlled by enzymes that are absent in rodents. Engle created models of transgenic mice whose cells produced CA19-9 using the expression of human enzymes (fucosyltransferase 3 and β1, 3-galactosyltransferase 5), and noted that all mice developed severe pancreatitis. The findings allow us to position CA19-9 as an attractive therapeutic target for the treatment of pancreatitis.
In mice, CA19-9 activates the immune system to repair damage from pancreatitis and at the same time triggers a cascade of biochemical reactions leading to the release of activated digestive enzymes from the pancreas and the rapid development of severe pancreatitis. The process is accompanied by hyperactivation of epidermal growth factor receptor (EGFR) receptors. As a result, inflammation transforms into cancer. In addition, CA19-9 significantly accelerates the growth of pancreatic tumors.
Pancreatitis is a necessary background for the development of pancreatic cancer. Blocking CA19-9 may prevent this transition in patients with pancreatitis. Engl's group demonstrated this in animal models by targeting CA19-9 antibodies and achieving a reduction in the severity of pancreatitis and even preventing its development.
A patent application for the use of antibodies to CA19-9 for the treatment and prevention of pancreatitis is under consideration.
Article by D. D. Engle et al. The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice is published in the journal Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to Cold Spring Harbor Laboratory: Sugars that coat proteins are a possible drug target for pancreatitis.