Can chronic stress boost cancer spread?

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In a breakthrough study, a team of researchers have shown how chronic stress can aid in cancer spread.

Chronic stress can increase our risk for heart disease and strokes. While it is also known to help cancer spread, how this works has remained a mystery.

The team from Cold Spring Harbor Laboratory (CSHL) in the US discovered that stress causes certain white blood cells called neutrophils to form sticky web-like structures that make body tissues more susceptible to metastasis.

The finding, published in the journal Cancer Cell, could point to new treatment strategies that stop cancer's spread before it starts.

"Stress is something we cannot really avoid in cancer patients. You can imagine if you are diagnosed, you cannot stop thinking about the disease or insurance or family. So it is very important to understand how stress works on us," said Xue-Yan He, a former postdoc in Cold Spring Harbor Laboratory (CSHL).

The team arrived at their discovery by mimicking chronic stress in mice with cancer. They first removed tumours that had been growing in mice's breasts and spreading cancer cells to their lungs. Next, they exposed the mice to stress.

"Saw this scary increase in metastatic lesions in these animals. It was up to a fourfold increase in metastasis," said Mikala Egeblad, Adjunct Professor at CSHL.

The team found that stress hormones called glucocorticoids acted on the neutrophils. These "stressed" neutrophils formed spider-web-like structures called NETs (neutrophil extracellular traps). NETs form when neutrophils expel DNA. Normally, they can defend us against invading microorganisms. However, in cancer, NETs create a metastasis-friendly environment.

To confirm that stress triggers NET formation, leading to increased metastasis, she performed three tests.

First, she removed neutrophils from the mice using antibodies. Next, she injected a NET-destroying drug into the animals. Lastly, she used mice whose neutrophils couldn't respond to glucocorticoids. Each test achieved similar results.

"The stressed mice no longer developed more metastasis," she said.

Notably, the team found that chronic stress caused NET formation to modify lung tissue even in mice without cancer.

"It's almost preparing your tissue for getting cancer," Egeblad explained.

"Reducing stress should be a component of cancer treatment and prevention," said CSHL Professor Linda Van Aelst.

The team also speculates that future drugs preventing NET formation could benefit patients whose cancer hasn't yet metastasised. Such new treatments could slow or stop cancer's spread, offering much-needed relief.

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