The study is the first to demonstrate, in an animal model, the direct effects of fragmented sleep on tumour growth and invasiveness. (Agencies)
"Fragmented sleep changes how the immune system deals with cancer in ways that make the disease more aggressive," said study director David Gozal, chairman of pediatrics at the University of Chicago Comer Children's Hospital.
"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," Gozal said.
Gozal 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 tumours within 9 to 12 days. Four weeks after inoculation the researchers evaluated the tumours.
They found that tumors from mice with fragmented sleep were twice as large, for both tumor types, than 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 tumours were much more aggressive and invaded surrounding tissues in mice with disrupted sleep.
The difference appeared to be driven by cells from the immune system, called tumour-associated macrophages (TAMs), which cluster at the site of tumours.
TAMs are a hallmark of the immune system's response to cancer. Some, labelled M1, promote a strong immune response and can eliminate tumours cells. Others, known as M2, suppress the immune response and instead promote the growth of new blood vessels - which encourages tumour growth.
Well-rested mice had primarily M1-type TAMs, concentrated in the core of the tumours. Sleep-fragmented mice had primarily M2-type TAMs, researchers said.
The study was published in the journal Cancer Research.
The study is the first to demonstrate, in an animal model, the direct effects of fragmented sleep on tumour growth and invasiveness.