Stress Linked to Increased Cancer Metastasis: Breakthrough Study Reveals the Role of Neutrophils
Stress is an unavoidable part of life, but its impact on our health can be detrimental. Not only does chronic stress increase the risk of heart disease and strokes, but it may also contribute to the spread of cancer. The exact mechanism behind this phenomenon has long remained a mystery, posing a significant challenge for cancer care. However, researchers at Cold Spring Harbor Laboratory (CSHL) may have made a groundbreaking discovery that sheds light on the relationship between stress and cancer metastasis.
Led by Xue-Yan He, a former postdoc in CSHL Adjunct Professor Mikala Egeblad’s lab, the team uncovered how stress can significantly increase cancer metastasis through the activation of white blood cells known as neutrophils. These neutrophils create web-like structures called neutrophil extracellular traps (NETs), which promote the spread of cancer cells. By simulating chronic stress in mice with cancer, the researchers observed a dramatic increase in metastatic lesions, linking stress hormones to the formation of NETs that foster a metastasis-friendly environment.
He explains, “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.” This understanding could pave the way for new treatment strategies aimed at preventing NET formation and ultimately halting cancer’s spread.
To investigate the relationship between stress and cancer metastasis, the team removed tumors from mice that had been growing in their breasts and spreading cancer cells to their lungs. They then exposed the mice to stress and were shocked by the results. Egeblad recalls, “She saw this scary increase in metastatic lesions in these animals. It was up to a fourfold increase in metastasis.”
Further analysis revealed that stress hormones called glucocorticoids acted on the neutrophils, causing them to form NETs. These structures, which are normally involved in defending the body against microorganisms, create an environment that is conducive to cancer spread. To confirm their findings, He 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 yielded similar results, with stressed mice no longer developing more metastasis.
Interestingly, the team also discovered that chronic stress caused NET formation to modify lung tissue even in mice without cancer. Egeblad explains, “It’s almost preparing your tissue for getting cancer.” This finding highlights the importance of stress reduction not only in cancer treatment but also in prevention.
The implications of this breakthrough study are significant. Reducing stress should be an integral component of cancer treatment and prevention, according to CSHL Professor Linda Van Aelst. Moreover, the researchers speculate that future drugs targeting NET formation could benefit patients whose cancer has not yet metastasized. These treatments could potentially slow or stop the spread of cancer cells, providing much-needed relief for patients.
While stress may be unavoidable, understanding its impact on cancer metastasis is crucial for developing effective treatment strategies. This groundbreaking study by CSHL researchers has shed light on the role of neutrophils and NETs in promoting cancer spread under conditions of chronic stress. By targeting NET formation, scientists may be able to develop new therapies that prevent metastasis and improve outcomes for cancer patients. In the meantime, reducing stress should be prioritized as an essential aspect of cancer care, emphasizing the importance of holistic approaches to treatment and prevention.
