How Stress Can Reawaken Dormant Cancer
Stress can lead to the return of cancer after treatment, new research finds.
Posted Dec 04, 2020
Everyone is experiencing increased stress during the pandemic, and some of us—doctors, nurses, workers who are suddenly unemployed, and people who have lost loved ones to the disease—are dealing with profound stress. The belief that psychological stress can increase the risk of cancer is widely shared, but the scientific studies to date have provided mixed evidence. Now a new study, published this week in the journal Science Translational Medicine, shows that stress can reactivate dormant tumor cells, and the researchers have pinpointed the biological mechanism.
According to the authors of this study, recurrence of tumors after they have been successfully treated or removed by surgery is one of the major causes of death in people who get cancer. The body’s defenses and cancer drugs can kill or stop the growth of a tumor and render any remaining tumor cells dormant. Unable to divide, these dormant tumor cells are harmless, but given the right conditions, the “sleeper” tumor cells can reawaken and grow.
Cell division is tightly regulated in all cells in the body, and biologists have a good understanding of this complex process. One way that cell division is stimulated is by protein signaling molecules, called—well, not very original—"growth factors." This new study on lung and ovarian cancer conducted in mice finds that a particular well-known growth factor, called "fibroblast growth factor," is produced after the animals are stressed, and this causes dormant tumor cells to become reactivated.
The surprising thing is what causes this flood of fibroblast growth factor that fuels the growth of dormant tumor cells after stress. The same blood cells that protect the body from infection and disease, white blood cells called neutrophils, are responsible for kicking off this unfortunate sequence of events. The neutrophils respond to stress hormones circulating in the body, which makes perfect sense for a cell that acts as the body’s first responder.
In response to the stress hormone, neutrophils release pro-inflammatory proteins to confront the disease threat, but this study finds that lipids inside these cells suffer collateral damage by oxidation from these proinflammatory proteins. The oxidized lipids leak out of the white blood cells and stimulate dormant tumor cells to start making fibroblast growth factor. The dormant tumor cells awaken in response and start to divide. This explains in detail how psychological stress can cause a resurgence of cancer.
In these experiments, which included cell culture and animal studies, stress was produced by adding stress hormones directly or by restraining mice four hours/day for five days, which is a well-established model of producing stress that is used in many psychological and physiological experiments. The results showed that stress hormone failed to cause dormant tumor cells to divide in genetically engineered mice that lacked the S100A8/A9 proinflammatory protein. Tumor revitalization by stress was also prevented if mice were treated with a drug that blocks the receptor on cells that detects stress hormones (beta2 adrenergic receptor).
Backing up these findings from animal research, the investigators measured the amount of the proinflammatory protein that sets off this chain of events (S100A8/A9) in the blood of patients after their lung cancer surgery. They observed that the levels of this pro-inflammatory protein in patients’ blood correlated with the length of time before they experienced a recurrence of the cancer.
Managing stress is important for health and wellbeing, but many times the factors causing the stress are beyond one’s control. This new research not only explains at a cellular and molecular level how dormant cancers are revitalized by stress, but by identifying the mechanisms, offers new ways to prevent the recurrence of tumors in cancer survivors. All that is needed is to provide a drug that inhibits that pro-inflammatory protein (S100A8/A9) or blocks the receptor on neutrophils that senses stress hormone.