Sleep apnea, and the recurrent lack of oxygen that it causes, may promote lung cancer growth and the ability of the cancer to spread. Researchers found that occasional low-oxygen conditions make cancer cells release tiny spheres, packed with cancer-promoting molecules, which travel to nearby tissues, signaling the need for growth.
The study, “Tumor Cell Malignant Properties Are Enhanced by Circulating Exosomes in Sleep Apnea,” was published in the journal CHEST.
Sleep apnea — interruption of breathing during sleep — is a known risk factor of cancer and early death. With this in mind, researchers at the University of Chicago and the University of Barcelona in Spain tested whether the repeated lack of oxygen caused by sleep apnea worsens lung cancer once it is already present.
The research team first simulated sleep apnea in mice with lung cancer by occasionally restricting oxygen. They then measured the presence of the spheres, known as exosomes, in the mice’s blood. Exosomes are used by cells to communicate with other cells by exchanging various types of molecules.
Repeat exposure to low oxygen levels increased the presence of exosomes in the blood. Along with this increase, the tumors grew in the mice faster, with cancer cells showing a higher ability to move within the body, compared to tumors in mice not on restricted oxygen. More cancer cells moving around means that the cancer is more likely to spread.
When the team gathered the released exosomes and placed them in dishes with lab-grown cells, the cells started changing their properties to a more cancer-like state. Finally, to test if the same could be true for humans, the team isolated exosomes from human patients with sleep apnea.
These human lung cancer cells, after exposure to the exosomes, were seen to divide faster and have a better ability to move around. Once patients were treated for their sleep apnea, however, their exosomes lost the ability to boost cancer growth.
“Over the past few years, exosomes have emerged as critically important players in intercellular communication,” David Gozal, MD, MBA, with the Pritzker School of Medicine at the University of Chicago and the study’s senior investigator, said in a press release.
“Notably, several studies have demonstrated the role of tumor exosomes in regulating major processes of tumor progression, such as angiogenesis [blood vessel formation], immune modulation, and metastasis,” he said.
To better understand how the exosomes promoted cancer, the team examined miRNAs found in the spheres. miRNAs are molecules that can change the activity of genes, and so the properties of a cell. They found 11 miRNAs that differed between normally breathing mice and those exposed to low oxygen levels. They could also track down the genes controlled by the miRNAs.
“There is no doubt,” said Gozal, “that improved understanding of the complex network of genes and cellular signaling transduction pathways regulated by exosomal miRNAs in the context of obstructive sleep apnea will augment our knowledge on its potential deleterious effects among cancer patients.”