November is Pancreatic Cancer Awareness Month: A new study from LIMR scientists unveils the cellular mechanisms that appear to promote pancreatitis and pancreatic cancer
A new study from the Lankenau Institute for Medical Research (LIMR), part of Main Line Health, demonstrated that elevated levels of a particular protein led to symptoms characteristic of pancreatitis, and when coupled with the presence of a genetic mutation, led to the development of pancreatic cancer. Their results could lead the way to a new therapeutic target to treat pancreatitis, a known risk factor for pancreatic cancer.
In the U.S., about 53,000 people will be diagnosed with pancreatic cancer in 2017, according to the American Cancer Society. Unfortunately, the disease has a one-year survival rate of only 20 percent, and a five-year survival rate of just seven percent.
The LIMR researchers centered their studies on the RNA-binding protein Human antigen R (HuR) that, in normal circumstances, helps maintain cells throughout the body in a healthy state. But when healthy cells are stressed from environmental insults (e.g., smoking, alcohol consumption), or in the case of tumor cells, from chemotherapy or nutrient depletion, HuR levels increase dramatically and regulate genes that promote an inflammatory microenvironment leading—the LIMR researchers discovered—to chronic pancreatitis, a disease in which the pancreas becomes inflamed.
After unveiling the link between HuR-mediated inflammation and pancreatitis-like symptoms, the scientists then set out to try to determine the cellular mechanism that leads from pancreatitis to pancreatic cancer.
“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,” said Professor Janet Sawicki, PhD, deputy director of LIMR and senior investigator of the study. “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.”
Weidan Peng, PhD, research assistant professor in Dr. Sawicki’s lab and the lead author of the study, noted: “These are exciting findings, because they offer proof-of-concept of a novel therapeutic target for pancreatitis—namely, mediation of HuR expression in the pancreas—that could, in turn, reduce the risk of pancreatic cancer.”
The researchers’ study, “Elevated HuR in pancreas promotes a pancreatitis-like inflammatory microenvironment that facilitates tumor development,” was published in a recent edition of the biomedical journal Molecular and Cellular Biology. Other authors of this paper include LIMR researchers Narumi Furuuchi, Ludmila Aslanukova and Yu-Hung Huang, as well as collaborators from the Sidney Kimmel Cancer Center at Thomas Jefferson University, and the University of Kansas Medical Center.
The research 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.