Chronic stress can cause cancer spread - study

No one lives a stress-free life, but too much of it can be very harmful to our health, as chronic stress can raise the risk of heart disease and strokes.

It may also help cancer spread, but this work has remained a mystery and a challenge for cancer care.

Chronic stress is a physiological process initiated by environmental and/or psychosocial factors. It affects memory, cognition, and behavior, as well as whole-body homeostasis, including the cardiovascular, gastrointestinal, and immune systems. 

Cancer patients, especially, have many sources of severe stress, including worrying about their prognosis and enduring weeks of therapy. 

Stress that cannot be avoided

Xue-Yan He, a former postdoctoral student in the Cold Spring Harbor Laboratory on Long Island in New York who worked in Prof. Mikala Egeblad’s lab, explained: “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.”

Now, he and Egeblad may have reached a breakthrough in understanding exactly that.

Working with Cold Harbor cancer researcher Prof. Linda Linda Van Aelst, the team discovered that stress causes white blood cells called neutrophils to form sticky web-like structures that make body tissues more susceptible to metastasis. The finding could point to new treatment strategies that stop cancer’s spread before it starts.

They have just published their findings in the journal Cancer Cell under the title “Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment.”

The team reached their conclusion by mimicking chronic stress in mice who had cancer. 

A breakthrough through research 

They first removed tumors that had been growing in mice’s breasts and spreading cancer cells to their lungs. Next, they exposed the mice to stress. “What we saw was shocking – a scary increase in metastatic lesions in these animals. It was up to a fourfold increase in metastasis,” Egeblad recalled. 

They found that stress hormones called glucocorticoids acted on the neutrophils. These “stressed” neutrophils formed spider-web-like structures that form when neutrophils expel DNA.

Normally, they can defend us against invading microorganisms, but in cancer, NETs create a metastasis-friendly environment.

To confirm that stress triggers NET formation that leads to increased metastasis, they performed three tests.

First, they removed neutrophils from the mice using antibodies. Next, they injected a NET-destroying drug into the animals. Lastly, they used mice whose neutrophils couldn’t respond to glucocorticoids. Each test achieved similar results. “The stressed mice no longer developed more metastasis;” 

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. To Van Aelst, the implication, though startling, is clear. “Reducing stress should be a component of cancer treatment and prevention."

The researchers also speculated that future drugs preventing NET formation could benefit patients whose cancer hasn’t yet metastasized.

Such new treatments could slow or stop cancer’s spread, offering much-needed relief.