La apnea del sueño puede incrementar la mortalidad en el cáncer de pulmón

A team of researchers of the University of Barcelona and the University of Chicago found that intermittent hypoxia, or irregular lack of air experienced by people with sleep apnea, can increase tumor growth by promoting the release of exosomes. The results of this study, with its main author being Isaac Almendros, researcher from the Department of Biomedicine of the UB, have been published in the journal CHEST.

Obstructive sleep apnea is associated with a major incidence of cancer and mortality. In order to understand this relation bettwe, this research study analysed the tumor cell growth in mice. Half of the mice experienced regular breathing patterns, while the other half of mice were exposed to intermittent hypoxia (IH) to simulate sleep apnea. The researchers found that mice exposed to hypoxia had an increase of exosomes, as well as changes in their gene content related to an increase of malignant properties of the lung cancer cells.

Exosomes are microscopic spferes 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. When exosomes increase in number and change their content, tumors become bigger and metastasize more easily.
The levels of variable oxygen in apnea provoke damage detected at a tissue level. Although many other confounding factors exist, sleep apnea is shown as an independent factor associated with adverce cancer outcomes. This study illustrates that exosomes, invigorated by intermittent hypoxia, can influence tumors by facilitating their growth and helping them spread through the body, making cancer potentially more dangerous for patients who suffer from sleep apnea.

According to the UB researcher Isaac Almendros, “this study helps understanding why sleep apnea can be a dramatic factor in cancer”. Also, “the continuation of this research line in mice research is to expose them to intermittent hypoxia combined with the fragmentation of sleep because this perturbance –typical sleep apnea- can contribute to increase cancer’s malignity”. The study, led by David Gozal, researcher of the University of Chicago, where professor Almendros carried the research out, results from a long collaboration with the team of UB professor Ramon Farré, who leads this research line at the University of Barcelona. At the same time, the release of exosomes in sleep apnea patients is being analysed by counting plasma exosomes.

Data showed that mice that were exposed to IH had an increase of cancer friendly exosomes. These exosomes increased the speed at which cancer cells replicated and promoted the movement of those cells throughout the body –to do so, they broke the endothelial barrier-, so they increased the possibilities of a metastasis.

When isolating the exosomes from mice exposed to IH, these exosomes promoted malignant cell properties in vitro. Furthermore, exosomes from actual patients with sleep apnea showed 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.

Researchers also analysed the miRNAs released by exosomes and found differences in the miRNA from mice exposed to IH compared with those with regular breathing patterns. Eleven discrete miRNAs were identified, along with their gene targets in lung cancer cells.

Reference:
Almendros, A. Khalyfa, W. Trzepizur, A. Gileles-Hillel, L. Huang, M. Akbarpour, J. Andrade, R. Farré, D. Gozal. «Tumor cell malignant properties are enhanced by circulating exosomes in sleep apnea». CHEST, November 2016. Doi:10.1016/j.chest.2016.08.1438

Image: saac Almendros, researcher from the Department of Biomedicine of the UB.