Whilst the effects of social and environmental factors on many aspects of health are relatively well understood, their influence on the progression of systemic cancer is much less well defined. A team of investigators led by scientists at The Ohio State University have now investigated the effect of an enriched environment – a more challenging setting that causes mild stress – on the growth of cancer in mice. The study found that an enriched environment – consisting of more complex housing, regular exposure to novel objects, and more exercise and social stimulation – led to a remarkable suppression of cancer proliferation in models of melanoma and colon cancer, even if delayed until the tumour was well established.
The researchers went on to identify the molecular pathways involved and discovered the enriched environment led to activation of a system known as the hypothalamic-sympathoneural-adipocyte (HSA) axis by brain-derived neurotrophic factor (BDNF). Activation of the HSA axis is proposed to increase sympathetic nervous system outflow to adipocytes, resulting ultimately in reduced secretion of leptin and increased secretion of adiponectin. The β-blocker, propanolol, was shown to inhibit the changes in circulating levels of leptin and adiponectin brought about by an enriched environment and also to block the inhibition of tumour growth, suggesting a link between β-adrenergic activity in white adipose tissue, circulating leptin/adiponectin levels and tumour growth.
The researchers propose that adipokines, released by white adipose tissue in response to hypothalamic BDNF-induced sympathetic outflow caused by mild stress, act as the major downstream effectors of a complex regulatory network leading to the antiproliferative phenotype. Direct gene transfer of BDNF was found to mimic the beneficial effects of an enriched environment, suggesting that either pharmacological or environmental induction of hypothalamic BDNF could slow the growth of tumours.
The study is published in the journal Cell.