Does Long-term Stress Promote The Spread of Cancer?

The risk of heart disease and strokes can rise with ongoing stress. It is also known to aid in the spread of cancer, though how this occurs is still unknown.

Researchers at the US’s Cold Spring Harbor Laboratory (CSHL) have found that stress increases the formation of sticky web-like structures by neutrophils, a kind of white blood cell that increases the susceptibility of bodily tissues to metastasis.

The discovery, which was reported in the journal Cancer Cell, may lead to novel therapeutic approaches that halt cancer’s spread before it even occurs.

“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).

By simulating chronic stress in cancer-stricken mice, the researchers were able to make their discovery. Initially, tumors that were expanding in the mice’s breasts and causing cancer cells to travel to their lungs were removed. The mice were then subjected 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 group discovered that the neutrophils were affected by glucocorticoids, which are stress hormones. These “stressed” neutrophils created NETs, or neutrophil extracellular traps, which resembled spiderwebs. DNA is released by neutrophils, forming NETs. They can typically protect us from invasive microbes. NETs, on the other hand, foster a metastasis-friendly environment in cancer.

She carried out three tests to verify that stress causes NET development, which increases metastasis.

She started by employing antibodies to eliminate neutrophils from the mice. She next gave the mice an injection of a medication that destroys NETs. Last but not least, she employed mice whose neutrophils were resistant to glucocorticoids. The outcomes of each test were comparable.

“The stressed mice no longer developed more metastasis,” she stated.

Notably, even in mice without cancer, the scientists discovered that long-term stress led to NET formation, which altered lung tissue.

According to Egeblad, “it’s almost like preparing your tissue for cancer.”

Professor Linda Van Aelst of CSHL stated, “Reducing stress should be a component of cancer treatment and prevention.”

Additionally, the team hypothesizes that individuals whose cancer has not yet spread may benefit from future medications that stop the production of NETs. Such novel medicines could provide much-needed respite by slowing or stopping the progression of cancer.