When mice with cancer get a boost in their social life and an upgrade in living conditions, their tumors shrink, and their cancers more often go into spontaneous remission Reported in the July 9th issue of the journal Cell, a Cell Press publication, these findings offer powerful new evidence of the critical role that social connection and an individual's mental state, may play in cancer.
"Animals' interaction with the environment has a profound influence on the growth of cancer – more than we knew was possible," said Matthew During of The Ohio State University.
It's not as if the animals' usual housing was all that bad. Laboratory mice are typically housed in groups of five or so, where they can have all the food they want and play all day. The enriched environments in the new study expanded living groups to 15 or 20 animals and provided them with more space and more things to play with and do – including toys, hiding places and running wheels.
When During and his colleague Lei Cao placed mice with cancer in that enriched environment, the animals tumor mass shrunk by an impressive 77 percent and the volume by 43 percent, the researchers report. Five percent of mice that had been given cancer showed no evidence of the disease after three weeks in their new home. That never happened in control animals kept in standard housing.
During says that the more complex social dimension in the new living arrangements was apparently key. The same improvements weren't seen in animals who only exercised more, so physical activity in and of itself wasn't the answer.
The animals did show lower levels of a hormone produced by fat called leptin, indicative of a significant shift in metabolism. Their immune systems also appeared to be "ramped up a bit," During said.
During and his colleague ultimately traced the effect to an axis from the brain to fat driven by an increase in a growth factor expressed in the hypothalamus called brain-derived neurotrophic factor (BDNF).
Further study showed that manipulations designed to increase BDNF levels also reduced tumor burden. In animals lacking BDNF, the benefits of an enriched environment evaporated.
The researchers say the findings lend favor to the view that low levels of stress, or certain kinds of stress, can be beneficial. "A lot of people think stress is bad, but our data show the animals aren't just happy. Antidepressants won't give you the same effect." In fact, the animals show higher levels of stress hormones known as glucocorticoids.
"The goal isn't to minimize stress, but to live a richer life, socially and physically," During said. "You want to be challenged."
The findings could ultimately lead to clinical advances in the way we tackle cancer and perhaps other diseases as well, whether through environmental modifications that offer mental and social stimulation or perhaps via a drug that mimics those experiences on a molecular level. It will be important to find out what it takes in humans to turn BDNF on.
"We're really showing that you can't look at a disease like cancer in isolation," During said. "For too long, physicians and other have stuck to what they know – surgery, chemo, radiotherapy. Traditionally working on the area of lifestyle and the brain has been a 'soft area.' This paper really suggests if we look at people more in terms of their perceptions of disease, their social interactions and environment, we could realize a profound influence on cancer. There's no reason to suspect our findings [in mice] won't be generalizable."
The researchers include Lei Cao, The Ohio State University, Columbus, OH, Weill Medical College of Cornell University, New York, NY; Xianglan Liu, The Ohio State University, Columbus, OH; En-Ju D. Lin, The Ohio State University, Columbus, OH; Chuansong Wang, The Ohio State University, Columbus, OH; Eugene Y. Choi, The Ohio State University, Columbus, OH; Veronique Riban, The Ohio State University, Columbus, OH; Benjamin Lin, Weill Medical College of Cornell University, New York, NY, and Matthew J. During, The Ohio State University, Columbus, OH , Weill Medical College of Cornell University, New York, NY, University of Auckland, Auckland, New Zealand.