Sleep apnea’s variable oxygen levels cause damage that is detectable at the tissue level. Although many other confounding factors exist, sleep apnea is shown to be an independent factor associated with adverse cancer outcomes. Now, a study from researchers led by the University of Chicago shows that intermittent hypoxia, or an irregular lack of air experienced by people with sleep apnea, can increase tumour growth by promoting the release of circulating exosomes. The team state that their findings show exosomes, invigorated by intermittent hypoxia, can influence tumours by facilitating their growth and helping them spread throughout the body, making cancer potentially more dangerous for patients who suffer from sleep apnea.
Previous studies show that exosomes are microscopic spheres that transport proteins, lipids, mRNAs, and miRNAs between cells, similar to courier messengers delivering packages. They play a central role in cell-to-cell communication and are involved in promoting cancer cell growth. Hypoxia can increase exosomal release and selectively modify exosome contents such as to enhance tumour proliferation and angiogenesis. The current study shows that the overall concentrations of plasma-isolated exosomes in intermittent hypoxia-exposed mice were significantly increased.
The current study utilises a mouse model of lung cancer in order to better understand the connection between sleep apnea and cancer. Half of the mice experienced regular breathing patterns, while the other half were exposed to intermittent hypoxia to simulate sleep apnea. Results show that exposing the mice to intermittent hypoxia increased the number of cancer friendly exosomes. Data findings show that these exosomes increased the speed at which cancer cells replicated and promoted the movement of those cells throughout the body, disrupting the endothelial barrier and increasing the likelihood of metastasis.
Results show the exosomes isolated from mice that had been exposed to intermittent hypoxia promoted malignant cell properties in vitro once extracted. Data findings show that exosomes from actual patients with sleep apnea exhibited the same effects on human cancer cells in culture when compared with exosomes from the same patients after treatment of their sleep apnea with CPAP.
The lab also examined miRNAs released by the exosomes and found differences in miRNA from mice exposed to intermittent hypoxia compared with those with regular breathing patterns. The team state that eleven discrete miRNAs were identified, along with their gene targets inside the lung cancer cells. They conclude that the fact intermittent hypoxia elicits altered exosome miRNA content and selectively enhances specific properties of tumour biology provides a strong impetus and rationale for future studies in both mice and humans.
The team surmise their findings suggest that exosomes participate in the increased tumour aggressiveness observed in patients with sleep apnea. For the future, the researchers state that improved understanding of the complex network of genes regulated by exosomal miRNAs in the context of obstructive sleep apnea will augment knowledge on its potential deleterious effects among cancer patients.
Source: University of Chicago