Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest human cancers without clinically effective treatment options. PDA is characterized by intense fibro-inflammatory stroma, poor vascularization, dysregulated nutrient levels, and rich deposition of extracellular matrix (ECM) components. The microenvironment of a pancreatic tumor is highly stromal, which means that the mass itself is composed primarily of connective tissue and non-cancerous immune cells. Hyaluronic acid or hyaluronan (HA) is a major stromal component and its accumulation has been shown to play a central role in promoting tumorigenesis and disease progression.
Hyaluronic acid, or HA, is a known presence in pancreatic tumors, but a new study by researchers at the University of Michigan Health Rogel Cancer Center shows that hyaluronic acid also acts as food for cancer cells.
The results were recently published in eLife and provide exciting insights into the growth of pancreatic cancer cells, pointing to new possibilities for treating them.
Principal Investigator Dr. Costas Lyssiotis and his study team examined pancreatic cancer metabolism in preclinical models: how cells obtain nutrients and the spectrum of nutrients they use to fuel growth and enable therapeutic resistance.
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Many people take hyaluronic acid supplements for its skin benefits, especially to relieve dry skin, reduce the appearance of fine lines and wrinkles, and speed wound healing.
It may also help relieve joint pain in people with osteoarthritis.
Hyaluronic acid is a substance naturally present in the skin, eyes and joints.
Its main function is to trap water inside tissue cells, keeping joints lubricated, which a recent study suggests may be the driving factor in the increase in cancerous pancreatic tumors.
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“The stroma occurs in the body’s natural healing process,” Lyssiotis explained.
“As these scars form, an abundance of hyaluronic acid is released.”
Hyaluronic acid, a polymer or long chain of sugars, attracts and retains water.
When there are a lot of them, pancreatic tumors become hyperdense, collapse veins and blood flow.
Lyssiotis says that these tumors then become very hard.
“It’s not that there aren’t any veins or arteries inside the tumor. But the vascular system there cannot withstand the extreme pressure.
Lyssiotis and his lab wanted to understand hyaluronic acid beyond its contribution to the physiological makeup of pancreatic cancer cells.
They looked at the density of these tumors and asked themselves: if cancer cells don’t have access to blood-derived nutrients, how do they get the nutrients that fuel cell growth and become tumors?
The cells that make up a tumor are a combination of many different cell types, some malignant, some not.
The microenvironment of a pancreatic tumor is mainly composed of connective tissue and non-cancerous immune cells.
New work from the lab indicates that one-way cells do this by scavenging hyaluronic acid itself.
“Hyaluronic acid doesn’t just affect tumors by creating this density, which makes it difficult to treat,” Lyssiotis said.
“It’s literally a chain of sugars. In retrospect, it makes sense that malignant cells also feed on hyaluronic acid.
According to Lyssiotis, this study demonstrates how well pancreatic cancer cells scavenge nutrients in order to maintain their survival and growth.
Symptoms of pancreatic cancer include abdominal pain that radiates to the back, loss of appetite, jaundice, light-colored stools, dark urine, or itchy skin.