The short term effects of poor sleep may be tiredness and a lack of concentration but there is far more serious long term damage on the immune system, say scientists.
Poor-quality sleep marked by frequent awakenings can speed cancer growth, increase tumour aggressiveness and dampen the immune system's ability to control or eradicate early cancers, according to a new study published online in the journal Cancer Research.
The study is the first to demonstrate, using an animal model, the direct effects of fragmented sleep on tumour growth and invasiveness, and it points to a biological mechanism that could serve as a potential target for therapy.
"It's not the tumour, it's the immune system," said study director David Gozal, MD, chairman of pediatrics at the University of Chicago Comer Children's Hospital. "Fragmented sleep changes how the immune system deals with cancer in ways that make the disease more aggressive."
"Fortunately, our study also points to a potential drug target," he said. "Toll-like receptor 4, a biological messenger, helps control activation of the innate immune system. It appears to be a lynchpin for the cancer-promoting effects of sleep loss. The effects of fragmented sleep that we focused on were not seen in mice that lacked this protein."
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Gozal, an authority on the consequences of sleep apnea, was struck by two recent studies linking apnoea to increased cancer mortality. So he and colleagues from the University of Chicago and the University of Louisville devised a series of experiments to measure the effects of disrupted sleep on cancer.
They used mice, housed in small groups. During the day - when mice normally sleep - a quiet, motorised brush moved through half of the cages every two minutes, forcing those mice to wake up and then go back to sleep. The rest of the mice were not disturbed.
After seven days in this setting, both groups of mice were injected with cells from one of two tumour types (TC-1 or 3LLC). All mice developed palpable tumors within 9 to 12 days. Four weeks after inoculation the researchers evaluated the tumours.
They found that tumours from mice with fragmented sleep were twice as large, for both tumour types, as those from mice that had slept normally. A follow-up experiment found that when tumour cells were implanted in the thigh muscle, which should help contain growth, the tumors were much more aggressive and invaded surrounding tissues in mice with disrupted sleep.
"In that setting, tumours are usually encased by a capsule of surrounding tissue, like a scar," Gozal said. "They form little spheres, with nice demarcation between cancerous and normal tissue. But in the fragmented-sleep mice, the tumours were much more invasive. They pushed through the capsule. They went into the muscle, into the bone. It was a mess."
"This study offers biological plausibility to the epidemiological associations between perturbed sleep and cancer outcomes," Gozal said. "The take home message is to take care of your sleep quality and quantity like you take care of your bank account."
"Considering the high prevalence of both sleep disorders and cancer in middle age or older populations," the authors wrote, "there are far-reaching implications."
Their next step is to determine whether sleep affects metastasis or resistance to cancer chemotherapy.