How Hyaluronic Acid Promotes Pancreatic Cancer Cell Growth Revealed

Hyaluronic acid is known to be present in pancreatic tumors. However, in a new study, researchers from the University of Michigan Roger Cancer Center and the University of Pennsylvania found that hyaluronic acid also acts as a food for cancer cells. The results provide new insights into how pancreatic cancer cells grow and point to new possibilities for the treatment of this cancer. The relevant findings were recently published in the eLife journal, and the paper was entitled "Hyaluronic acid fuels pancreatic cancer cell growth".

Dr. Costas Lyssiotis, corresponding author of the paper from University of Michigan Roger Cancer Center, said, "A core driven theme in my research laboratory is that pancreatic cancer does not respond to common treatments. We need to think about the challenge in different ways." He and his team studied pancreatic cancer metabolism in preclinical models: how cells acquire nutrients and what nutrients they use to promote growth and achieve therapeutic resistance.

The tumor microenvironment is composed of many different cell types, some of which are malignant cells, and others are not malignant cells. The pancreatic tumor microenvironment is highly stromal, meaning that the tumor mass itself is mainly composed of connective tissue and non-cancerous immune cells. Lyssiotis explained, "The matrix arises during natural scarring of the body. As these scars form, large amounts of hyaluronic acid are released. "

Hyaluronic acid is a kind of sugar chain, very good at attracting and retaining water. When it is abundant, the pancreatic tumor becomes excessively dense, allowing the veins and blood flow to collapse. Lyssiotis says these tumors become very hard. This is not to say that there are no veins or arteries in the pancreatic tumor, but the existing vessels cannot withstand extreme pressure.

Most studies of hyaluronic acid in pancreatic cancer have focused on its role in forming this dense. A recent unsuccessful clinical trial even explored ways to degrade hyaluronic acid and release tumor pressure to allow vasodilatation and delivery of drugs, which are however often difficult to deliver given the lack of blood flow.

Lyssiotis and his laboratory wanted to understand hyaluronic acid, not just its contribution to the physiological constitution of pancreatic cancer cells. They considered the density of these tumors and wondered: if cancer cells do not acquire nutrients from the blood, how do they acquire nutrients that promote cell growth and become tumors?

This new study shows that one way pancreatic cancer cells do this is by clearing hyaluronan itself. Lyssiotis says, "Hyaluronic acid affects tumors not only by forming this dense, although this does make it difficult to treat. It's actually a sugar chain. Looking back, it makes sense that malignant cells also feed on hyaluronic acid."

Lyssiotis says this study demonstrates how well pancreatic cancer cells are able to take up nutrients in order to maintain their survival and growth.

The study was published in collaboration with a research team led by Dr. Kathryn Wellen at the University of Pennsylvania. Her laboratory showed that inhibition of this carbohydrate clearance pathway prevented tumor growth. This study provides new opportunities to better understand the nuances of pancreatic cancer.

Lyssiotis said, "Hyaluronic acid in pancreatic cancer has been studied for 20 years, and no one has thought of seeing if it will become a nutrient for cancer cells. We want to analyze this idea in more depth to see if it represents a therapeutic weakness that can be targeted using drugs."

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