Researchers decode origin of inflammation-driven pancreatic cancer

Volume 2, Issue 4, 2013

Summary

Findings point to ways to identify patients at risk of pancreatic cancer and potential drug therapies that might reverse the process.

Photograph showing Peter Storz, Ph.D., a Mayo Clinic Cancer Center biochemist and molecular biologist

Peter Storz, Ph.D.

Photograph showing Massimo Raimondo, M.D., a Mayo Clinic gastroenterologist

Massimo Raimondo, M.D.

Researchers at the Mayo Clinic Cancer Center in Florida have discovered the process by which pancreatitis can morph into pancreatic cancer. These findings may point to ways to identify pancreatitis patients who are at risk of pancreatic cancer and to potential drug therapies that might reverse the process.

The study, published in the Aug. 5, 2013, edition of the Journal of Cell Biology, maps how inflammation pushes acinar cells in the pancreas — those that produce digestive enzymes — to transform into duct-like cells. As these acinar cells change, they can acquire mutations that can contribute to the development of pancreatic cancer.

"We don't know why these cells reprogram themselves, but it may be because producing enzymes in an organ that is injured due to inflammation may cause more damage," said senior author Peter Storz, Ph.D., a Mayo Clinic Cancer Center biochemist and molecular biologist. "The good news, however, is that this process is reversible, and we identified a number of molecules involved in this pathway that might be targeted to help push these new duct-like cells back into acinar cells, thus eliminating the risk of cancer development."

Mayo Clinic scientists are testing the ability of drugs already on the market to reverse this cellular transformation in the pancreas in mice models of human pancreatic cancer. Dr. Storz's research team traced the pathway leading from inflammation in the pancreas to development of cancer in the pancreas. They followed what happened once white blood cells called macrophages responded to an inflamed pancreas.

"The belief in the field has been that macrophages were there to remove damaged cells in the organ," Dr. Storz said. "We found they weren't that benign. In fact, we discovered that macrophages themselves drive the transformation and provide the setting for development of cancer."

The research team also discovered that fluid from an inflamed pancreas contains signaling molecules that induce acinar cells to transform into duct-like cells. Study co-author Massimo Raimondo, M.D., a gastroenterologist, is part of a Mayo Clinic team that has developed a method to collect this fluid from the pancreas during a routine upper endoscopy.

"We want to also investigate whether these two enzymes can serve as an early warning system, a marker of pancreatic cancer risk, in patients with pancreatitis," Dr. Storz said. "Our hope is that we can detect that risk before cancer happens and use a treatment that reverses any possibility that pancreatic cancer will develop."