Chronic stress effects help cancer spread, researchers find

Chronic stress accelerates cancer growth in mice, according to a paper published in Nature Communications this week. The finding points to potential treatment targets to slow the progression of cancer to other organs.

The paper revealed findings from several studies, mostly on mice, conducted by a team of researchers from Monash University.

Chronic stress refers to prolonged, repeated exposure to stressful situations, such as caring for a sick relative for a long period of time. To mimic the way people feel under significant stress, researchers restrained mice with breast cancer tumours, to make them feel like they couldn’t cope with their circumstances.

Over time, the mice developed an increase in the number and size of of their lymphatic vessels – a network of vessels that transports fluid around the body. This enhanced the spread of cancer cells to new sites, a process called cancer progression or metastasis.

By blocking the activity of proteins that detect stress, or those that enhance the formation of lymphatic vessels, researchers found they could reduce the spread of cancer cells in the mice.

What stress does to the body

The research focused on metastasis of breast cancer to other parts of the body, building on previous findings that neurological stress hinders our defence against disease.

Previous findings from human studies have shown poorer cancer survival in people exposed to stressful life experiences and those more prone to stress.

Another clinical trial showed better survival rates for breast cancer patients in remission who participated in a 12-month intervention with strategies to reduce stress, improve mood and alter health behaviours.

Everyday stressful experiences pose a threat to the body’s natural balance. This is because stress activates the sympathetic nervous system (SNS), which is responsible for what we know as the fight or flight response.

Under stress, the SNS releases higher levels of neurotransmitters. These hormones, such as epinephrine, signal to other cells to activate physiological flight or flight responses, such as a faster heart rate. This is important during times of threat because it makes us more alert and increases physiological functions needed for rapid reactions.

But as shown in the Nature Communications study, chronic periods of stress can lead to changes in the lymphatic system. These include an increase in the number of vessels in the tumours as well as the size of these vessels. These changes are associated with the spread of cancer cells to lymph nodes and distant organs, such as the lung.

Clinically, we know that when cancer cells have spread through blood vessels into the lymph vessels, that’s an important indicator of poorer prognosis. Preventing this could improve survival rates.

It’s not so simple

The latest findings have obvious treatment implications, which include using drugs to block stress responses that lead to changes in lymphatic vessels. But blocking any part of a natural pathway can promote a cascade of negative effects.

The study reported that a number of patients on drugs often used to treat anxiety and high blood pressure (beta blockers that block the actions of adrenaline) were less likely to have secondary cancer that had spread from its primary site.

This is good news, but more work is needed before such interventions can be further tested.

This is because the lymphatic system is important in our immune response and manipulating any of its mechanisms could carry potential harms. These include limiting the immune system’s ability to respond to the cancer in the first place.

It could also increase the risk of lymphedema – swelling in one or more extremities – that results from impaired flow of the lymphatic system.

Although the authors did show supportive data from human clinical subjects, the bulk of the work was done in mouse models. Results from mice experiments don’t always translate to human systems, so further clinical testing is an essential step in translating these findings.

Overall, though, the study points the way to potentially helping prevent cancer spreading so far from the original site that it’s too hard to treat.