A new study conducted by US-based Lankenau Institute for Medical Research (LIMR), part of Main Line Health, has revealed the cellular mechanisms that promote pancreatitis and pancreatic cancer.
The LIMR researchers have found that elevated levels of a particular protein, Human antigen R (HuR), can lead to symptoms characteristic of pancreatitis, and when combined with the presence of a genetic mutation facilitates the development of pancreatic cancer.
The research outcomes are expected to lead the way for the development of a new therapeutic target that would treat pancreatitis, a disease in which the pancreas of a person becomes inflamed.
The study authors focused on the evaluation of the ribonucleic acid (RNA)-binding HuR protein, which helps maintain cells throughout a person’s body in a healthy state under usual circumstances.
However, the research revealed that when these healthy cells are stressed from environmental factors, such as smoking and alcohol consumption, or in the case of tumour cells from chemotherapy or nutrient depletion, HuR levels increase significantly and regulate genes that promote an inflammatory microenvironment.
This inflammatory microenvironment, in turn, leads to chronic pancreatitis, a known risk factor for pancreatic cancer.
The researchers also tried to identify the cellular mechanism that leads from pancreatitis to pancreatic cancer.
LIMR deputy director Dr Janet Sawicki said: “We found in our preclinical studies that when the pancreas is inflamed due to elevated HuR and a genetic mutation in the K-ras gene is present, the incidence of pancreatic ductal adenocarcinoma increased more than three-fold when compared to the presence of the K-ras mutation alone.
“We found that HuR overexpression alone does not cause cancer, but when it is paired with an oncogenic initiating event such as a K-ras mutation, the incidence of pancreatic cancer increases.”
Titled ‘Elevated HuR in pancreas promotes a pancreatitis-like inflammatory microenvironment that facilitates tumour development’, the LIMR study was funded by the National Institutes of Health, the W.W. Smith Charitable Foundation, the Mary Halinski Pancreatic Cancer Research Fund and the Lankenau Medical Center Foundation.