PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Fragmented sleep accelerates cancer growth

Sleepy immune system tips balance toward tumors

2014-01-27
(Press-News.org) Contact information: John Easton
john.easton@uchospitals.edu
773-795-5225
University of Chicago Medical Center
Fragmented sleep accelerates cancer growth Sleepy immune system tips balance toward tumors Poor-quality sleep marked by frequent awakenings can speed cancer growth, increase tumor aggressiveness and dampen the immune system's ability to control or eradicate early cancers, according to a new study published online January 21, 2014, in the journal Cancer Research.

The study is the first to demonstrate, in an animal model, the direct effects of fragmented sleep on tumor growth and invasiveness, and it points to a biological mechanism that could serve as a potential target for therapy.

"It's not the tumor, 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."

Gozal, an authority on the consequences of sleep apnea, was struck by two recent studies linking apnea 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, motorized 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 tumor types (TC-1 or 3LLC). All mice developed palpable tumors within 9 to 12 days. Four weeks after inoculation the researchers evaluated the tumors.

They found that tumors from mice with fragmented sleep were twice as large, for both tumor types, as those from mice that had slept normally. A follow-up experiment found that 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.

"In that setting, tumors 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 tumors were much more invasive. They pushed through the capsule. They went into the muscle, into the bone. It was a mess."

The difference appeared to be driven by cells from the immune system, called tumor-associated macrophages (TAMs), which cluster at the site of tumors. TAMs are a hallmark of the immune system's response to cancer, but they can respond in a variety of ways, depending on chemical signals they receive. Some, labelled M1, promote a strong immune response and can eliminate tumors cells. Others, known as M2, suppress the immune response and instead promote the growth of new blood vessels—which encourages tumor growth.

Well-rested mice had primarily M1-type TAMs, concentrated in the core of the tumors. Sleep-fragmented mice had primarily M2-type TAMs. These were abundant, especially around the periphery of the tumors. The sleep-disrupted mice also had high levels of toll-like receptor 4 (TLR4).

Three key molecules are part of the signaling pathway that appeared to be tilting macrophages toward M2: TLR4 and two downstream signals called MYD88 and TRIF. So 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.

Taking TLR4 out of the picture resulted in major curtailment of tumor growth. "When we injected tumor cells into mice that lacked TLR4," Gozal said, "the differences between undisturbed and sleep-fragmented mice disappeared."

"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."

The Centers for Disease Control and Prevention estimate that about 70 million Americans suffer from chronic sleep problems. "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.

### The National Institutes of Health funded this study. Additional authors include Fahed Hakim, Yang Wang, Shelley Zhang, Jiamao Zheng, Alba Carreras, Abdelnaby Khlayfa and Isaac Almendros from the University of Chicago; and Esma S. Yolcu and Haval Shirwan from the University of Louisville.


ELSE PRESS RELEASES FROM THIS DATE:

Migrants' children as well integrated as Swedes' children

2014-01-27
"You can't compare apples and oranges. For the most part, children whose parents immigrated to Sweden in the 1960s and 1970s have a working-class background, while the children of the majority population ...

Brain biomarker shows promise in heart

2014-01-27
A biomarker widely used to diagnose brain injury has shown early promise ...

A silk coat for diamonds makes sleek new imaging and drug delivery tool

2014-01-27
WASHINGTON, Jan. 27—Silk and diamonds aren't just for ties and jewelry anymore. They're ingredients for a new kind of tiny glowing particle that could provide doctors and researchers with a novel technique ...

'Element of surprise' explains why motorcycles are a greater traffic hazard than cars

2014-01-27
"I didn't see it, because I wasn't expecting it there," might be the more accurate ...

Genomics for judges: Educating Illinois judges on how genetic info impacts court decisions

2014-01-27
PUBLIC RELEASE DATE: 27-Jan-2014 [ | E-mail ] var addthis_pub="eurekalert"; var addthis_options = "favorites, delicious, digg, facebook, twitter, google, newsvine, reddit, slashdot, stumbleupon, buzz, more" Share Contact: Nicholas Vasi nvasi@illinois.edu Institute for Genomic Biology, University of Illinois at Urbana-Champaign Genomics for judges: Educating Illinois judges on how genetic info impacts court decisions New seminar prepares judges to deal with legal questions involving DNA sequencing, analysis, and related technologies in the courts today ...

Early tumor response from stereotactic radiosurgery predicts outcome

2014-01-27
The response of a patient with metastatic brain tumors to treatment with stereotactic radiosurgery in the first six-to-twelve weeks can indicate whether follow-up treatments ...

Swiss cheese crystal, or high-tech sponge?

2014-01-27
BUFFALO, N.Y. — The sponges of the future will do more than clean house. Picture this, for example: Doctors use a tiny ...

Researchers tune in to protein pairs

2014-01-27
Rice University scientists have created a way to interpret interactions among pairs of task-oriented proteins that relay signals. The goal is to learn how the proteins ...

Common crop pesticides kill honeybee larvae in the hive

2014-01-27
Four pesticides commonly used on crops to kill insects and fungi also kill honeybee larvae within their hives, according to Penn State and University of Florida researchers. The team also found that N-methyl-2-pyrrolidone ...

Do brain connections help shape religious beliefs?

2014-01-27
New Rochelle, NY, January 27, 2014—Building on previous evidence showing that religious belief involves cognitive activity that can be mapped to specific brain regions, a new study has ...

LAST 30 PRESS RELEASES:

Novel treatment combination improves progression-free survival in metastatic, estrogen-receptor-positive HER-2-negative breast cancer

ESMO 2025: Trial results show belzutifan shrinks rare neuroendocrine tumors and improves symptoms in patients

ESMO 2025: Dual targeted therapy shows promise in previously treated advanced kidney cancer patients

New generation of Antibody-Drug Conjugates (ADCs) shows unprecedented promise in early-stage disease

Sylvester Cancer Tip Sheet for October 2025

Three science and technology leaders elected to Hertz Foundation Board of Directors

Jump Trading CSO Kevin Bowers elected to Hertz Foundation Board of Directors

Former Inscripta CEO Sri Kosaraju elected to Hertz Foundation Board of Directors

Citadel’s Jordan Chetty elected to Hertz Foundation Board of Directors

McGill research flags Montreal snow dump, inactive landfills as major methane polluters

A lightweight and rapid bidirectional search algorithm

Eighty-five years of big tree history available in one place for the first time

MIT invents human brain model with six major cell types to enable personalized disease research, drug discovery

Health and economic air quality co-benefits of stringent climate policies

How immune cells deliver their deadly cargo

How the brain becomes a better listener: How focus enhances sound processing

Processed fats found in margarines unlikely to affect heart health

Scientists discover how leukemia cells evade treatment

Sandra Shi MD, MPH, named 2025 STAT Wunderkind

Treating liver disease with microscopic nanoparticles

Chemicals might be hitching a ride on nanoplastics to enter your skin

Pregnant patients with preexisting high cholesterol may have elevated CV risk

UC stroke experts discuss current and future use of AI tools in research and treatment

The Southern Ocean’s low-salinity water locked away CO2 for decades, but...

OHSU researchers develop functional eggs from human skin cells

Most users cannot identify AI bias, even in training data

Hurricane outages: Analysis details the where, and who, of increased future power cuts

Craters on surface of melanoma cells found to serve as sites for tumor killing

Research Spotlight: Mapping overlooked challenges in stroke recovery

Geographic and temporal patterns of screening for breast, cervical, and colorectal cancer in the US

[Press-News.org] Fragmented sleep accelerates cancer growth
Sleepy immune system tips balance toward tumors