Poor Sleep Quality Increases Cancer Aggression

Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages (TAMs), according to a new study.

Researchers at the University of Chicago (IL, USA) and the University of Louisville (KY, USA) fragmented the sleep of mice by waking them up every two minutes during sleep for a period of week, before injecting them with cancerous cells. All mice developed tumors within twelve days of injection and their tumors were measured after four weeks. The results showed that there was an increase in tumor size, weight, and invasiveness in the fragmented sleep mice, compared to control animals.

Furthermore, the sleep-deprived mice had increased counts of TAMs, immune cells that respond differently to cancer depending on the chemical signals they receive. While M1 TAMs promote an immune response and eliminate tumor cells, M2 TAMs suppress an immune response and encourage tumor growth. The fragmented sleep induced a TAM polarity shift so that there was more M2 expression than M1 expression in tumors, which appears to be triggered by three key molecules: upstream signaling by toll-like receptor 4 (TLR4), and downstream signals by MYD88 and TRIF channels.

To examine the impact of the three signaling paths, the researchers injected tumor cells into a series of mice that were unable to produce one of these three proteins and subjected them to fragmented sleep. Tumor growth was slightly reduced in mice lacking MYD88 or TRIF, but in mice lacking TLR4, tumor growth was no greater than in mice with undisturbed sleep, indicating that TLR4 is a major contributor to tumor growth in fragmented sleep. The study was published online on January 21, 2014, in Cancer Research.

“When tumor 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,” said senior author David Gozal, MD, chairman of pediatrics at the UC Comer Children’s Hospital. “In that setting, tumors are usually encased by a capsule of surrounding tissue, like a scar. They form little spheres, with nice demarcation between cancerous and normal tissue. But in the fragmented-sleep mice, the tumors were much more invasive. They pushed through the capsule. They went into the muscle, into the bone. It was a mess.”

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