Chronic, or long-term stress can lead to a multitude of illnesses and diseases, including digestive issues, heart disease, and high blood pressure. Prolonged periods of stress can cause headaches, difficulty sleeping, depression, and anxiety. In addition, chronic stress weakens the immune response, making affected individuals more susceptible to infection.
The immune system plays a pivotal role in preventing cancer by eliminating abnormal cells before they develop into cancer. Studies have correlated stress to both cancer growth and metastasis. Despite many links between stress and cancer, whether chronic stress, on its own, can actually cause stress remains unclear.
A study published in a recent issue of Cell addresses the underlying role of chronic stress in metastasis, the spread of cancer cells from the area where it initiated to a distant part of the body. Using mouse models, the researchers demonstrated that chronic stress accelerated the growth rate of breast tumors and increased the rate of metastasis to the lung.
Additional studies showed that chronic stress altered some critical components of the microenvironment in the lung. Fibronectin, a protein that facilitates biological processes, including tumor progression, accumulates in the lung following chronic stress. In addition, mice experiencing chronic stress had fewer T cells, the immune cells the body uses to fight cancer, infiltrating their lungs. Finally, the researchers found that neutrophils, immune cells that form an initial line of defense against foreign invaders, entered the lung more frequently when exposed to chronic stress.
To further interrogate the role of neutrophils entering the lung following stress, the researchers depleted them and found that stress-induced metastasis ceased. Next, they saw that stress altered the circadian rhythm in neutrophils, facilitated by the release of glucocorticoids, a type of steroid with anti-inflammatory and immunosuppressive effects. Additional experiments showed that chronic stress could not induce neutrophil infiltration or metastasis without neutrophil-specific glucocorticoids.
The researchers conclude that glucocorticoids released in response to chronic stress promote a metastatic-favorable microenvironment. The authors suggest that further work could identify these pathways as targets for preventing metastatic recurrence in cancer survivors.
Notably, cancer survivors represent a unique cohort of patients, one expected to endure a significant amount of stress. Thus, therapies that potentially augment the adverse effects of stress could prove highly valuable for cancer survivors.
Sources: Front Oncol, Future Oncol, Cell
