OKLAHOMA CITY – Pancreatic cancer, one of the most difficult cancers to treat, is closely associated with obesity, which can be influenced by diet. With a five-year, $2.6 million grant from the National Cancer Institute, a University of Oklahoma researcher will investigate how a diet high in saturated fats may contribute to tumor growth by weakening the body’s anti-tumor immune response and changing how cancer cells use fats.
In preliminary studies, principal investigator Kamiya Mehla, Ph.D., and her team found that mice with pancreatic cancer that ate a lard-based high-fat diet developed more aggressive tumors than mice that ate a diet with the same number of calories but with much less fat.
“When anti-tumor immune cells take in a lot of fat, they become functionally impaired and their anti-tumor activity goes down. The tumor cells are forcing the immune cells to take in more fat – we want to understand how that is happening,” said Mehla, associate professor of oncology science in the OU College of Medicine and a research member of OU Health Stephenson Cancer Center on the OU Harold Hamm Health Campus.
The researchers are examining whether excess fat directly changes the metabolism of pancreatic cancer cells. They hypothesize that a diet high in monounsaturated fats may give tumors greater access to fats, fueling their survival and uncontrolled growth. Further, the study is investigating how tumor cells exposed to excess fat may interfere with the body’s ability to fight cancer, both within the tumor and elsewhere in the body.
The proposed study builds on preliminary findings that mice with pancreatic tumors fed a lard-based high-fat diet had increased numbers of a type of immune cell called granulocytes. The researchers found that these cells can interfere with the immune system’s ability to fight cancer. In experiments, reducing their activity improved the ability of other immune cells to attack pancreatic cancer cells.
“We want to understand how a high-fat diet affects both the immune system’s ability to fight cancer and the tumor’s ability to grow,” Mehla said.
Alongside experiments in mice, the team will analyze human pancreatic cancer tissue to look for metabolic changes that may be related to the processes observed in the animal models. Ultimately, the goal is to better understand how diet, obesity, immune function and tumor metabolism interact in pancreatic cancer.
Leah Hoffman Anderson, Ph.D., a professor in the Department of Nutritional Sciences at the OU College of Allied Health, is serving as a co-investigator on the grant, lending her expertise as a registered and licensed dietitian. She also has experience working with patients who have cachexia, a condition characterized by severe muscle and weight loss that is common in pancreatic cancer. Cachexia can weaken patients and make it more difficult for them to tolerate cancer treatment.
Anderson said dietitians have typically encouraged their patients with cachexia to eat high-calorie foods in an attempt to maintain their weight. She said this research could eventually help dietitians better understand how to meet the nutritional needs of patients with pancreatic cancer while accounting for the possible effects of dietary fat on tumor growth.
“We want to understand how we can best support patients’ nutritional needs while learning more about how diet may affect their cancer,” she said. “Many patients and their families ask what they should or shouldn’t be eating. We hope this research will help us provide patients with guidance based on scientific evidence and give them a greater sense of control.”
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About the project
Research reported in this press release is supported by the National Cancer Institute, a component of the National Institutes of Health, under award number U01CA296929-01A1. Additional co-investigators on the grant are Jed E. Friedman, Ph.D., Pankaj Singh, Ph.D., and Sixia Chen, Ph.D. The preliminary research was funded by a team science grant from the OU Health Stephenson Cancer Center and OU Health Harold Hamm Diabetes Center. Support for the OU Health Stephenson Cancer Center’s programs and activities includes funding from the Tobacco Settlement Endowment Trust (TSET), among other sources.
About the University of Oklahoma
Founded in 1890, the University of Oklahoma is a public research university with campuses in Norman, Oklahoma City and Tulsa. As the state’s flagship university, OU serves the educational, cultural, economic and healthcare needs of the state, region and nation. In Oklahoma City, the OU Harold Hamm Health Campus is one of the nation’s few academic health centers with seven health profession colleges located on the same campus. The OU Harold Hamm Health Campus serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs spanning Oklahoma City and Tulsa and is the leading research institution in Oklahoma. For more information about the OU Harold Hamm Health Campus, visit www.ouhsc.edu .