Master switch that triggers pancreatic cancer identified
Washington: A new study led by an Indian-origin researcher suggests that a master regulator protein may explain the development of aberrant cell growth in the pancreas spurred by inflammation.
Inflammation of the pancreas, or pancreatitis, is a leading reason for hospital admission, and chronic pancreatitis is a risk factor for cancer of the pancreas.
Acute pancreatitis is caused by alcohol abuse, gallstones, and autoimmune disorders.
When things go wrong, inflammatory pancreatitis happens, and the change from an acute state to a chronic state can lead to cancer.
When a patient recovers from pancreatitis, the change in cell fate reverts to the original cell type. But, if the pancreatitis is chronic, changed cells stay changed.
Broadly speaking, two cellular compartments are important in a normal pancreas, endocrine cells, which produce hormones including insulin, and exocrine cells – acinar and ductal -- which make and secrete digestive enzymes.
Anil Rustgi, MD, Chief, Division of Gastroenterology from the Perelman School of Medicine at the University of Pennsylvania, and colleagues studied the molecular changes of exocrine cells during inflammation, so-called acinar-ductal metaplasia (ADM), a prelude to pancreatic ductal adenocarcinoma.
They used cell lineage tracing to follow what happens to the regulator protein called Prrx1 as cells change characteristics. Another protein, Sox9, which is downstream of Prrx1 in the cell signal pathway, is also important in understanding how pancreatic cancer forms, as the group has established the first link of Prrx1 to Sox9.
The findings suggest that Prrx1 and Sox9 influence the emergence of an intermediate cell type that can give rise to cancer.
"We hope that studies like this one that identifies key molecules and pathways that govern the cancerous fate of cells can be used as diagnostic predictors of treatment outcome and severity for cancer," says Rustgi, MD, Chief, Division of Gastroenterology.
The study has been published online in Genes and Development.