HMN 2026: How Aggressive brain tumors build protective ‘sugar shield’ to survive extreme stress

For the first time, researchers have identified a previously unrecognized metabolic defense mechanism in aggressive brain tumors: a sugar-rich shield that surrounds tumor cells and protects them against a particularly destructive form of cell death.

Aggressive brain tumors grow in an extreme environment characterized by oxygen and nutrient deficiencies, low pH and chronic cellular stress. Inside the tumor, conditions would normally damage or kill healthy cells, yet tumor cells adapt in ways that make them highly resilient. At the same time, these tumors are often resistant to currently available treatments.

In a study led by Lund University, published in Nature Cell Biology, researchers now show that tumor cells in aggressive brain tumors—including glioblastoma and metastases in the central nervous system—can avoid cell death by building up a sugar-rich surface layer around themselves, a mechanism not previously described.

“This changes our understanding of how aggressive brain tumors adapt to survive in the extreme tumor environment in the brain,” says Mattias Belting, professor of oncology at Lund University and senior neuro-oncology consultant at Skåne University Hospital, who led the study.

The sugar shield acts as a protective filter that limits the uptake of lipid particles from the surroundings—lipids that could otherwise be toxic in the tumor’s internal environment. In this way, cancer cells can avoid ferroptosis, a particularly destructive form of cell death. During ferroptosis, certain lipids undergo oxidation—in simple terms, they “turn rancid”—ultimately causing catastrophic cell damage and collapse.

At the molecular level, this sugar shield consists of long sugar chains that accumulate on the tumor cell surface. The researchers show that this structure is particularly rich in a complex sugar structure called chondroitin sulfate, which thickens the sugar shield and protects tumor cells from toxic lipids.

A double layer of metabolic protection against cell death

Tumor cells rely on not one but several survival strategies. In addition to the protective sugar shield, they store lipids in small droplets within the cell. These lipid droplets act as metabolic storage buffers—a sink that captures harmful lipids and prevents them from damaging the cell.

“We found that these two defense mechanisms—the sugar shield and the lipid droplets—cooperate. That led us to ask what would happen if you eliminate both at the same time,” says Anna Bång-Rudenstam, doctoral researcher and medical student at Lund University and first author of the study.

The researchers developed experimental strategies to impair the formation of chondroitin sulfate—the key component that builds up the tumor cell’s protective sugar shield—while simultaneously blocking the cell’s ability to store lipids in lipid droplets. When both defense systems were simultaneously disrupted, the tumor cells collapsed. The lipid particles could neither be kept out nor stored, which led to rapid cell death by ferroptosis.

“The experimental combination treatment attacks the tumor cells’ defense mechanisms. When they disappear, the tumor cells become highly vulnerable to oxidized lipids and ferroptosis,” says Bång-Rudenstam.

The results are based on analysis of tumor material from patients, including cells isolated immediately after brain surgery, as well as organoids—three-dimensional tumor models that more closely reflect tumor behavior in the patient. The researchers also found that the same sugar shield observed in glioblastoma is present in metastases to the central nervous system from malignant melanoma, lung cancer and kidney cancer.

“In the long term, we hope that these findings can help inform the development of more effective treatment strategies for this severely affected patient group,” says Belting.

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