“Freezing” Hyaluronic Acid Reprograms Brain Cancer Cells To Prevent Tumor Growth
Scientists have found a way to stop brain cancer cells spreading by essentially “freezing” a key molecule in the brain.
Brain cancer remains one of the most formidable challenges in oncology, with glioblastoma standing out as the most aggressive and deadly form, carrying a median patient survival time of less than 15 months. Glioblastoma is notorious for its ability to infiltrate healthy brain tissue, making complete removal nearly impossible.
Now, scientists at the University of Cambridge have uncovered a new way to block glioblastoma’s spread – not by killing tumor cells, but by altering their environment so they stop moving altogether. The findings, published in Royal Society Open Science, open the door to a treatment strategy that could reprogram cancer cells and potentially reduce recurrence.
The central role of hyaluronic acid
The brain’s supporting structure, known as the extracellular matrix, is a complex environment made up of proteins, sugars and other molecules. One of its most important components is hyaluronic acid (HA), a sugar-like polymer that provides the brain with its cushioning and structural properties.
The Cambridge team found that glioblastoma cells exploit HA’s flexibility to spread. HA molecules naturally twist and bend, adopting shapes that allow them to bind to CD44, a receptor located on the surface of cancer cells. Once activated, CD44 triggers signals that drive invasion and migration into surrounding brain tissue.
Professor Melinda Duer from Cambridge’s Yusuf Hamied Department of Chemistry, who led the research, explained: “Fundamentally, HA molecules need to be flexible to bind to cancer cell receptors. If you stop HA from being flexible, you stop cancer cells from spreading.”
Freezing molecules to stop cancer in its tracks
Using nuclear magnetic resonance spectroscopy, the researchers studied how HA interacts with glioblastoma cells. They discovered that when HA molecules were chemically cross-linked – effectively “frozen” into a rigid shape – they lost the ability to bind to CD44.
Glioblastoma cells that normally spread rapidly across the brain were reprogrammed into a dormant state. They stopped migrating and invading, even though they remained alive. Importantly, this effect was observed even at low concentrations of HA, suggesting the cells were not physically trapped but instead signaled to switch off their invasive behavior.
“The remarkable thing is that we didn’t have to kill the cells – we simply changed their environment, and they gave up trying to escape and invade neighboring tissue,” said Duer.
Glioblastoma presents unique treatment challenges. While surgery can remove the bulk of the tumor, stray cancer cells often remain embedded deep in the brain, triggering regrowth within months. Chemotherapy has limited penetration, and radiotherapy merely delays recurrence.
The new Cambridge approach offers a different strategy: instead of targeting the tumor cells directly, it focuses on modifying the tumor’s surroundings – the extracellular matrix. By making HA inflexible, researchers can essentially switch glioblastoma cells into a dormant mode, preventing them from infiltrating the brain.
“Nobody has ever tried to change cancer outcomes by changing the matrix around the tumor,” Duer explained. “This is the first example where a matrix-based therapy could be used to reprogram cancer cells.”
The work may also explain why glioblastoma often reappears at the surgical site. After tumor removal, fluid build-up – or edema – commonly occurs. This extra fluid dilutes HA, making it more flexible and potentially creating conditions that allow cancer cells to spread again.
If HA could be chemically stabilized after surgery, recurrence might be reduced. This insight points toward new possibilities for biomaterials or injectable therapies designed to lock HA in place at vulnerable sites in the brain.
Beyond brain cancer and towards clinical use
While the current study focuses on glioblastoma, the principle may extend to other cancers. Many solid tumors, from breast to pancreatic cancers, also rely on their surrounding extracellular matrix to drive invasion.
“Because our approach doesn’t require drugs to enter every single cancer cell, it could in principle work for many solid tumors where the surrounding matrix drives invasion,” Duer said. “Cancer cells behave the way they do in part because of their environment. If you change their environment, you can change the cells.”
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The research is still at an early stage. The team plans to conduct further experiments in animal models to confirm whether this matrix-based therapy can slow or prevent tumor growth in living systems. If successful, the approach could eventually progress to clinical trials.
Challenges remain, including how best to deliver treatments that can modify HA in the brain safely and precisely. Researchers will also need to determine whether the effect lasts long enough to provide meaningful protection against recurrence.
The concept of “reprogramming” cancer cells by targeting their environment rather than the cells themselves is gaining traction in oncology. For decades, cancer therapy has largely focused on killing tumor cells outright – through surgery, radiation or cytotoxic drugs. This work from Cambridge adds compelling evidence that reshaping the extracellular matrix could become a viable therapeutic pathway.
“This could be a real opportunity to slow glioblastoma progression,” said Duer. “And because our approach doesn’t require drugs to enter every single cancer cell, it could, in principle, work for many solid tumors where the surrounding matrix drives invasion.”
“Cancer cells behave the way they do in part because of their environment. If you change their environment, you can change the cells.”
Reference: Bashtanova U, Kuraite A, Rajan R, Duer M. Molecular flexibility of hyaluronic acid has a profound effect on invasion of cancer cells. R Soc Open Sci. 2025;12(8):251036. doi: 10.1098/rsos.251036
This article is a rework of a press release issued by the University of Cambridge. Material has been edited for length and content.
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