From Medscape Medical News
Zosia Chustecka
July 12, 2010 — Tumors grew more slowly and some even disappeared when mice with cancer were housed in an "enriched environment," where they had more space and more things to do.
"Simply placing the animals in a more complex living environment" produced effects "profound enough to significantly influence the growth of highly malignant cancers," researchers suggest.
The study is reported in the July 9 issue of Cell.
The researchers, led by Matthew During, MD, ScD, from Ohio State University, in Columbus, have previously shown that an enriched environment is good for the brain and can protect mice against cerebral insults such as epilepsy and neurotoxins.
The latest results show that such stimulation is also good for the body. "The same enriched environment also activates pathways that reduce the proliferative state with respect to cancer," Dr. During told Medscape Medical News.
"We believe that our results suggest that people should be challenged socially and physically, perhaps engage in team sports or competitive activities involving larger social groups, in addition to increased physical activity," he said.
"It means we shouldn't simply be avoiding stress but rather making our lives richer, more complex, more challenging, and a little stressful."
Its relevance to human cancer is highly questionable.
However, when asked about the study, Maurie Markman, MD, professor of medicine and chair of gynecologic medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston, who has an oncology videoblog on Medscape Medical News, answered with a "no comment."
"This is a mouse model and like all such artificial models, its relevance to human cancer is highly questionable," Dr. Markman said.
Significant Reduction in Cancer Burden
The enriched environment significantly reduced the cancer burden in 2 different mouse models: syngeneic melanoma and colon cancer.
Tumor mass shrank by 77% and tumor volume by 43%, and after 3 weeks in their new housing, 5% of mice showed no evidence of cancer.
No such changes were seen in a control group of mice in regular housing.
"Our results demonstrate that living in an enriched environment leads to a significant inhibition of cancer growth," the researchers conclude.
The fact that such an effect was seen even though the enriched environment was introduced after the establishment of the peripheral tumor suggests that there is "potential therapeutic relevance," the researchers note.
"This approach may have therapeutic significance in people who already have cancer," Dr. During said.
The team notes that serum from mice housed in the enriched environment was markedly lower in leptin than that from control mice; the environment was also shown to inhibit cancer proliferation in vitro.
In addition, the mice housed in the enriched environment showed:
* a small but significant increase in serum corticosterone, consistent with mild stress and elevation of the hypothalamus–pituitary axis
* activation of the hypothalamus with induction of immediate early genes, including brain-derived neurotrophic factor (BDNF)
* enhanced activity of natural killer cells.
The researchers propose that the biologic mechanism involved centers of activation of the hypothalamic–sympathoneural–adipocyte axis. More specifically, they suggest that environmental stimuli induce the expression of hypothalamic BDNF expression, and that this leads to sympathoneural activation. The elevated sympathetic drive activates adipocytes, which leads to a reduced production of leptin and release of adipokines, which have both direct mitogenic and antimitogenic activity and can also influence peripheral tumor growth indirectly through its effects on angiogenesis.
In addition, the researchers note that "direct transfer of BDNF can mimic the antiproliferative effects" of an enriched environment, and they suggest that either environmental or direct molecular approaches to inducing hypothalamic BNDF expression have therapeutic potential.
Dr. During noted that one approach that his team is now pursuing is the development of a defective viral vector expressing BDNF, which might have therapeutic potential in humans.
The authors have disclosed no relevant financial relationships.
Cell. 2010;142;52-64. Abstract
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