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Exploring the Link Between Obesity and Pancreatic Cancer

There is a strong correlation between obesity and increased pancreatic cancer risk. Researchers want to understand why. 
Michael VanSaun

June 02, 2020

According to the American Cancer Society, people who are obese are about 20% more likely to develop pancreatic cancer and are more likely to have a poorer prognosis compared to non-obese people. Excess body weight causes chronic inflammation in adipose tissue as well as throughout the body. Over time, chronic inflammation is known to alter cellular function as well as induce DNA damage in our cells, both of which promote cancer development and progression.

Researcher Michael VanSaun, PhD, studies the mechanisms linking obesity and pancreatic cancer. A member of The University of Kansas Cancer Center’s Cancer Biology research program, Dr. VanSaun’s pre-clinical efforts stem from his fatty liver disease research.

“In our preclinical studies, we found that colon cancer in overweight mice metastasized to the liver to a much greater extent and mice fed a high-fat diet had a significantly higher tumor load than a normal lean mouse. This led to the theory that, obesity can directly influence the severity of cancer,” Dr. VanSaun said.

Pancreatic cancer is another cancer type that metastasizes to the liver, and so Dr. VanSaun applied obesity to his pancreatic cancer models with similar results.

“Obese mice developed massive tumors and lean mice developed tiny tumors,” he said. “Solely attributable to consuming a high fat diet, nothing else.”

The next step is pinpointing a specific mechanism that drives the cancer progression. The fat may give us a clue. Fat doesn’t just store excess energy. It plays an active role in our physiology and can communicate with other cells by releasing adipokines, or factors produced in the fat.

“Understanding the crosstalk between the fat and cancer may reveal novel mechanisms of cancer progression,” Dr. VanSaun said.

Lean fat can release ‘good’ factors that help regulate glucose levels as well as fatty acid breakdown. Yet, obese fat eventually becomes inflamed and it can release cancer-promoting factors. Dr. VanSaun and his lab has also homed in on a protein hormone, adiponectin, which is released from lean fat, but not obese.

“Our mouse studies showed that adiponectin can slow the growth and progression of pancreatic cancer. In obese mice, once adiponectin secretion goes away and the protective factor is lost, the cancer grows faster,” Dr. VanSaun said. They are currently exploring ways to add back this protective factor.

Turns out, the more the fat cells give, the more the cancer cells take. Researchers are also investigating the circumstances surrounding cachexia, a syndrome causing extreme weight and fat loss that affects people in late-stage pancreatic cancer. It is estimated that nearly one-third of cancer deaths can be attributed to cachexia. According to Dr. VanSaun, as the cancer cells gather strength and grow, they start to talk back to the fat cells. Pancreatic cancer cells can leech the fat cells’ nutrients away, using the energy to drive their own growth.

“In a lean, healthy individual, a lot of this crosstalk is suppressed. But for an obese person, the increased crosstalk drives the aggressiveness of the tumor and speeds up cancer progression,” Dr. VanSaun said. “Interrupting this crosstalk is potentially a key for at least slowing down the progression of the disease.”


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