Biologists Discover How Pancreatic Tumors Lead to Weight Loss

Source: Massachusetts Institute of Technology

Summary: A new study offers insight into how patients with pancreatic cancer usually experience significant weight loss, which can begin very early in the disease.

Patients with pancreatic cancer usually experience significant weight loss, which can begin very early in the disease. They are sometimes given replacement enzymes to help them gain weight. Previously it was found that muscle starts breaking down very early in pancreatic cancer patients, usually long before any other signs of the disease appear. Still unknown was how this tissue wasting process occurs. One hypothesis was that pancreatic tumors overproduce some kind of signaling factor, such as a hormone, that circulates in the bloodstream and promotes the breakdown of muscle and fat. Researchers from MIT and Dana-Farber Cancer Institute found that weight loss occurs due to a reduction in key pancreatic enzymes that normally help digest food. When the researchers treated these mice with replacement enzymes, they were surprised to find that while the mice did regain weight. The study findings were published in the journal Nature.

Pancreatic cancer

Axial CT image with i.v. contrast. Macrocystic adenocarcinoma of the pancreatic head. Credit: CC0 Public Domain

The research team discovered that even very tiny, early-stage pancreatic tumors can impair the production of key digestive enzymes. Mice with these early-stage tumors lost weight even though they ate the same amount of food as normal mice. These mice were unable to digest all of their food, so they went into a starvation mode where the body begins to break down other tissues, especially fat. They found that when they implanted pancreatic tumor cells elsewhere in the body, this weight loss did not occur. That suggests the tumor cells are not secreting a weight-loss factor that circulates in the bloodstream; instead, they only stimulate tissue wasting when they are in the pancreas.

Assoc. Prof. Vander Heiden said, “From a mechanistic standpoint, this study reveals a very different way to think about what could be causing at least some weight loss in pancreatic cancer, suggesting that not all weight loss is the same across different cancers.”

More Information: Laura V. Danai et al, “Altered exocrine function can drive adipose wasting in early pancreatic cancer”, Nature (2018). DOI:10.1038/s41586-018-0235-7 

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