Stress and Cancer
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By Corinna Wu

All Stressed Out

A challenging environment may slow cancer growth

By Corinna Wu

Stress has often been considered unhealthy, and a contributing factor in the development of heart disease and cancer. But a study in the July 9 issue of Cell shows that a little stress might actually play a role in helping to suppress cancer growth.

Neuroscientist Matthew During of the Ohio State University Comprehensive Cancer Center, in Columbus, and his colleagues studied two groups of male mice. The control group lived in standard laboratory housing with five animals per cage. The others lived in groups of 18 to 20 in a much larger enclosure that was filled with toys, tunnels, nesting material and running wheels. “It’s both socially more complex and physically more complex,” During says. “All of those things add up to some mild stress,” which could be measured in elevated levels of a hormone, corticosterone, in the mice.

The researchers injected the mice with melanoma cells and found that the animals living in the more complex environment had smaller tumors than those of animals in standard housing, and 17 percent didn’t have any tumors at all after six weeks. The enriched environment was also associated with reduced tumor growth and prolonged survival in mice injected with colon cancer cells. Even after the tumors had been established, they grew more slowly in mice living in the enriched environment.

Investigating further, the researchers identified what they consider “a new stress pathway” that allows the brain to talk to fat cells. The more enriching, yet stressful, conditions triggered an increase in a protein called brain-derived neurotrophic factor (BDNF) within a mouse’s hypothalamus, a part of the brain. This, in turn, switched off production of leptin, a hormone produced by fat cells that regulates appetite and metabolism. “That hormone stimulates the growth of the cancer, so when we activate this pathway, and we stop the release of this hormone, we’re essentially starving the cancer,” During says.

A certain level of stress is probably healthy—for mice and for humans, During says. But distinguishing between good and bad stress is difficult, especially in people. “Some people thrive on a certain level of stress, and others are incapacitated by a similar level,” says Suzanne Conzen, a medical oncologist at the University of Chicago who has found evidence that stress arising from social isolation accelerates breast cancer growth in mice and rats. Her findings and the new results suggest that the relationship between external stress and tumor growth is complex, Conzen says, but “there’s no question that there’s some link between the environment, the brain, the neuroendocrine system and tumor biology.” The next steps are to find out how the pathway works on a molecular level and whether the same pathway that exists in mice also exists in people.