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Cold exposure stops tumor growth in mice by sequestering glucose stores

Continuous exposure to 4°C (39°F) for 20 days inhibited tumor growth and improved survival in mice with five different types of cancer cells


3 August 2022

A brown fat cell, surrounded by capillaries, captured through a color scanning electron micrograph. Activation of brown fat through exposure to cold can cause it to burn glucose, which cancerous tumor cells depend on for growth


Low temperatures might inhibit the growth of cancer cells, according to research done in mice and a person with Hodgkin’s lymphoma.

Exposure to low temperatures is thought to cause brown fat cells to burn glucose, the dominant energy source for cancer cells.

Some existing cancer treatments interrupt glucose uptake to slow or prevent tumor growth. These tend to be administered through medication, rather than exposure of the entire body to cold therapy. Medications may have more side effects and complex administration regimens, relative to cold therapy.

To test the potential of cold therapy, yihai cao at the Karolinska Institute in Sweden and colleagues implanted five different types of cancer cells into a group of mice. Some of the rodents were then continuously exposed to very low temperatures, but above freezing, for 20 days.

This exposure activated the mice’s brown adipose tissue, which burns energy instead of storing it, reducing the tumors’ energy supply.

These mice had considerable tumor inhibition and a survival rate that was almost double that of mice that received no treatment.

“This is really something new: It doesn’t directly target cancer cells, but rather alters the overall metabolism in the body to affect tumors,” says Cao.

To eliminate the possibility that the tumor suppression was due to something other than cold therapy, Cao and his team intervened in several ways. After surgically removing brown fat from cold-exposed mice, or turning off the gene by which brown fat generates heat, there was no tumor inhibition.

Inhibition was also absent when the mice were fed a high-glucose diet, suggesting that tumor growth was inhibited by a lack of glucose. The team also performed genetic analysis on the cold-exposed tumors and found a decrease in markers associated with glucose consumption.

In a second part of the experiment, Cao and his team exposed a group of six healthy human volunteers to 16 °C (61 °F) for 2 to 6 hours a day for two weeks. Similar to the mice, the volunteers’ brown fat tissue was activated.

The researchers then continuously exposed a person with Hodgkin lymphoma to 72 °F (22 °C) for seven days. Not only was his brown fat activated, but his tumors also consumed less glucose during this period.

The results are strong, but more research is needed, both in animals and in humans with tumors, he says. Katiuscia Bianchi at the Barts Cancer Institute in London.

According to Tardito Saverio at the Beatson Institute in Glasgow, UK, the results of tumor growth in mice are “surprising”. But since this treatment will most likely be given in combination with chemotherapy, it could negatively affect the chemotherapy drugs, she says, which should be ruled out before undertaking any concurrent treatment.

Cao himself admits that genetic variation in people’s brown fat and its response to cold may make the treatment unsuitable for some. People with advanced-stage cancer who have already lost weight, so may not be able to risk losing more through brown fat-driven energy intake, he says.

Magazine reference: Nature, DOI: 10.1038/s41586-022-05030-3


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