Intermittent Hypoxia Promotes Lung Tumor Cell Aggressiveness
IH-induced exosomes from mice significantly promote TC1 malignant properties
TUESDAY, Nov. 22, 2016 (HealthDay News) -- Circulating exosomes released under intermittent hypoxia (IH) conditions, which characterize obstructive sleep apnea (OSA), promote lung tumor cell aggressiveness, according to a study published in the November issue of CHEST.
Isaac Almendros, Ph.D., from the University of Chicago, and colleagues randomized C57/B6 male mice to six weeks of either IH or room air. After two weeks of IH, a subgroup was injected with TC1 lung carcinoma cells in the left flank. Mouse plasma exosomes and those from 10 adult human patients with OSA (before and after six weeks of treatment) were cocultured with mouse TC1 and human adenocarcinoma cell lines. To identify targets, the authors assessed malignant tumor properties and micro-RNA (miRNA), exosomal content, and transcriptomic effect of exosomes on TC1 cells in vitro.
The researchers found that TC1 malignant properties were significantly promoted by application of IH-induced exosomes from either IH-exposed tumor-bearing or non-tumor-bearing mice. Exosomes from patients with OSA significantly enhanced proliferation and migration of human adenocarcinoma cells before versus after adherent treatment. In IH-exposed mice there were 11 distinct miRNAs, and their gene targets were identified in TC1 cells.
"Circulating exosomes released under IH conditions in vivo selectively enhance specific properties of lung tumor cell cultures," the authors write. "Thus, plasma exosomes participate in the increased tumor aggressiveness observed in patients with OSA."