How Stress Could Make Cancer Spread

New research in mice may pinpoint how chronic stress can fuel the spread of cancer. The study found evidence that stress can induce changes to certain immune cells that inadvertently make it easier for cancer cells to metastasize and invade other parts of the body. The findings emphasize the need to manage stress following a cancer diagnosis, the scientists say, and could even help efforts to find new treatments.

The research was led by scientists at Cold Springs Harbor Laboratory in New York. Chronic stress has long been considered a risk factor for many health problems, including heart disease, headaches, and trouble sleeping. There’s also some research suggesting that stress can raise cancer risk or worsen outcomes in people already diagnosed with it, though there’s a lot about this connection that’s unclear. Since stress can make us more likely to develop other unhealthy habits, like drinking more alcohol, for instance, it might only indirectly increase our vulnerability to cancer.

The study authors decided to see if they could detect clear biological changes in mice with cancer exposed to chronic stress. The mice were made to develop cancer tumors in their breast tissue, and then some of the cells were moved over to the lungs, mimicking the process of metastasis.

Compared to control mice, the researchers found, the cancers grew much faster in the lungs of stressed mice. And when they looked closer, they found evidence that stress hormones were affecting the behavior of neutrophils, immune cells that are one of the first lines of defense against infection and other bodily threats. Specifically, stress seemed to induce the formation of spider web-like structures called NETs (neutrophil extracellular traps). NETs are typically used by neutrophils to engulf germs, but the team theorizes that they can somehow also create a friendlier home for cancer cells to metastasize.

To test their hypothesis, the team conducted various experiments that cleared neutrophils or NETs from the mice, or made their neutrophils entirely unresponsive to stress hormones. And across all these scenarios, they found that stress no longer acted like an accelerant to the mice’s cancers, providing more evidence that neutrophils and their NETs are the key factors behind this connection. They also found evidence that NETs can make lung tissue more fertile ground for cancer in general, even in mice without cancer.

“Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment,” the authors wrote in their paper, published Thursday in the journal Cancer Cell.

The findings would have to be validated by other research, especially in humans, before we can conclusively tie neutrophils and NETs to the scene of the crime. And it’s possible that there are other mechanisms involved that allow stress to aid the formation and spread of cancer. But the results do support the idea that keeping stress in check is particularly important for cancer patients. And down the line, the researchers speculate that it might be possible to safely develop NET-destroying drugs that can slow or prevent cancers from growing out of control.

“Reducing stress should be a component of cancer treatment and prevention,” said senior study author Mikala Egeblad in a statement from Cold Springs Harbor Laboratory.