Stress Creates a 4-Fold Increase in Spread of Cancer: Study
A breakthrough discovery links stress hormones with a fourfold surge in the spread of cancer, shedding light on why patients under severe stress often have lower survival rates.
“There’s probably very few situations that are as stressful as being diagnosed with cancer and undergoing cancer treatment,” Mikala Egeblad, cancer researcher and senior author of the study.
Understanding the stress–cancer link may open up new ways to protect patients from the adverse effects of stress as part of cancer care.
An Accidental Discovery Prompts More Research
The team of scientists from Cold Spring Harbor Laboratory (CSHL) found that glucocorticoids—a type of stress hormone—play a role in creating a metastasis-friendly environment.
The Egeblad lab, which relocated to Johns Hopkins University, studies how the communication between tumors and the immune system affects tumor growth and metastasis in mice. Researchers discovered the connection accidentally, noticing faster tumor growth in mice they had unintentionally stressed by a change in housing.
The phenomenon prompted further research on chronic stress exposure and how it can encourage the spread of cancer, according to first author Xue-Yan He, who was a postdoctoral fellow at CSHL and is now an assistant professor at the Washington University School of Medicine.
Ms. He investigated this connection with a mice study that mimicked chronic stress, leading to startling observations: an increase in tumor lesions and up to a fourfold surge in the spread of cancer.
‘Spiderweb’ Structures Encourage Cancer Cells
According to the study published in Cancer Cell, the size of mammary tumors approximately doubled, and the rate of metastasis to the lungs increased between two- and fourfold compared with control mice not exposed to stress.
The researchers found that chronic stress impacts neutrophils, a type of white blood cell, causing an increase in neutrophil activation in the tissues where the cancer cells go.
When looking at lung tissue, the researchers found that chronic stress had altered the body’s internal environment in a way that could promote cancer growth by increasing neutrophils and then reducing T-cells, immune cells that kill cancer cells.
“We also found more extracellular matrix; this is a protein [network] that can support cancer cell growth.” Extracellular matrix helps cells attach to nearby cells and plays a vital role in cell growth and movement.
Ms. Egeblad explained that the neutrophils in the tissues formed spiderweb-like structures called neutrophil extracellular traps (NETs). Essentially, these traps are sticky webs of DNA meant to trap pathogens. However, in the case of cancer, NETs do not serve their usual protective role.
Instead, according to Ms. Egeblad and Ms. He, it appears that the NETs, induced by stress, encourage the growth of breast cancer cells that reach the lungs. “Our work shows how chronic stress activates neutrophils, helping cancer cells grow,” added Ms. He.
To confirm that glucocorticoids drive NET formation, leading to increased metastasis, the researchers performed three tests, each interfering with this pathway. First, they removed neutrophils from the mice using antibodies. Next, they injected a NET-dissolving enzyme. Lastly, they used mice whose neutrophils couldn’t respond to glucocorticoids.
According to Ms. He, each test achieved similar results: Depleting the neutrophils stopped stress-induced metastasis.
Chronic Stress Primes the Body for Developing Cancer
“Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment,” the study authors wrote.
Unexpectedly, the study also showed that chronic stress can cause NETs to form and change lung tissues in mice without cancer, essentially preparing the body for cancer.
While this study highlights why managing severe stress is critical to cancer treatment, it also points to potential therapeutics that could target the formation of NETs or block the receptors for glucocorticoids.
“The next major directions that I see is understanding how much of this applies to humans and what can we do to to inhibit the stress in first, our animal models, and then eventually in patients,” said Ms. Egeblad.
She also hopes that understanding the stress response in patients will pave the way for better treatment and increased survival rates.
Unraveling the Deadly Stress-Cancer Alliance
Stress is unavoidable for someone navigating a cancer diagnosis. Many patients cite treatment decisions—and the surrounding uncertainty, anxiety, and even regret—as a source of distress, according to a 2023 study published in Scientific Reports.
The Annual Review of Psychology, researchers shared decades of data showing how stress reduction techniques improve outcomes for cancer patients. Techniques for stress management included:
- Breathwork: This involves deep, slow breathing while concentrating on filling the lungs and relaxing muscles.
- Progressive muscle relaxation: This technique involves tightening and then relaxing muscles. Most people start at either the toes or the head and progressively relax all the muscles across the body.
- Meditation: With this technique, you can learn to relax your mind and concentrate on an inner sense of calm.
- Yoga: Yoga focuses the mind on breathing and posture to promote relaxation and reduce fatigue.
Many of the findings in the review paper involved cognitive behavioral therapy (CBT) with a counselor, which focuses on actively changing thoughts and behavior. Patients were also taught to distinguish between stressors that are within their control and those that are not.
For stressors that feel like they are out of someone’s control, such as the uncertainties that come with facing a cancer care plan, relaxation techniques with social support seem to help patients manage anxiety.
Engaging with support groups and connecting with peers facing similar struggles provides a support network. Sharing experiences creates a sense of belonging, diminishing the isolation that can accompany cancer.
