Pancreatic Cancer Cells Feed on Hyaluronic Acid

Hyaluronic acid is a binding molecule found abundantly in the skin that gives it elasticity and moisture. It is present in high concentrations in the skin, joints, and eyes.

Hyaluronic Acid (HA) is also known for its presence in pancreatic tumors, but a new study conducted by researchers at the University of Michigan Rogel Cancer Center showed that hyaluronic acid also acts as food for cancer cells. The findings published in the scientific journal eLife shed light on how pancreatic cancer cells grow and point to new possibilities for treatment.

NOTE: This scientific study and article do not imply that taking or supplementing hyaluronic acid triggers cancer. They explain the mechanism by which cancer cells use a compound that is already naturally abundant in the body. Like normal cells, cancer cells use countless molecules to sustain their lives and continue multiplying, as well as to interact with other cells and the immune system. However, the types and concentrations of molecules used by cancer cells can differ from those used by normal cells. Much basic scientific research in oncology is carried out to identify these differences.

A Critical Building Block for Pancreatic Cancer Cells

Study leader Costas Lyssioyis says, “The main motivation for this study is that pancreatic cancer does not respond to common treatment approaches. We need to think differently about this challenge.” Lyssioyis and his team study pancreatic cancer metabolism in laboratory experimental models: how cells obtain nutrients and the range of nutrients they use to grow and develop resistance to treatments.

The tumor microenvironment contains many types of cells, some cancerous and some noncancerous. The microenvironment of a pancreatic tumor is one of the richest tumor microenvironments and is highly stromal (a mass made up mostly of connective tissue and noncancerous immune cells). Lyssiotis explains: “Stroma develops during the natural process of scarring (wound healing). As these scars form, a great deal of hyaluronic acid is secreted.”

Hyaluronic acid – a polymer or long chain of sugar – is excellent at attracting and retaining water. When there is a great deal of it, pancreatic tumors become hyperdense (containing denser tissue than the tissue around them), with blocked vessels and impaired blood flow. Lyssiotis says these tumors become very hard. “It is not that there are no blood vessels or arteries within the tumor, but the vascular system cannot withstand the excessive pressure.”

Most studies of hyaluronic acid in pancreatic cancer focus on its role in creating this density. A recently unsuccessful clinical trial even explored ways to break down hyaluronic acid and release pressure on tumors, allowing the vascular system to expand and drugs to be delivered, which is generally difficult because of the lack of blood flow.

Lyssiotis and his team wanted to understand hyaluronic acid beyond its contribution to the physiological formation of pancreatic cancer cells. They considered the density of these tumors and wondered: If cancer cells cannot access nutrients from the blood because of impaired circulation, how do they obtain nutrients to grow and become tumors?

The team’s new study suggests that one way cells do this is by feeding on hyaluronic acid. “Hyaluronic acid does not affect tumors only by creating this density that makes treatment difficult. It is literally a chain of sugar. In retrospect, it makes sense that malignant cells also feed on hyaluronic acid.” Lyssiotis says this study only demonstrates how pancreatic cells collect nutrients to continue surviving and growing.

"We have added another example to a growing body of evidence for nutrients and pathways that we did not think cancer cells would use to feed themselves."

Cancer Cells Do Not Grow When Feeding Is Blocked

It was published jointly with a team led by Kathryn Wellen at the University of Pennsylvania. Wellen’s team showed that blocking the sugar-feeding pathway inhibited tumor growth. Together, these two studies open up new possibilities for a better understanding of the finer details of pancreatic cancer.

Lyssiotis said of their research, “People have been studying hyaluronic acid in pancreatic cancer for 20 years, and no one had previously considered whether it could be a nutrient for cancer cells. We will explore this idea further and see whether we can identify a therapeutic vulnerability that can be targeted with a drug.”