title: Tumor Cell Malignant Properties Are Enhanced by Circulating Exosomes in Sleep Apnea.
abstract: BACKGROUND
  OSA is associated with increased cancer incidence and mortality. Exosomes are vesicles secreted by most cells. They are released into the bloodstream and play a role in tumor progression and metastasis. We evaluated whether the chronic intermittent hypoxia (IH) that characterizes OSA leads to release of tumor-promoting exosomes in the circulation.
  
  
  METHODS
  C57/B6 male mice were randomized to 6 weeks of IH or room air (RA). A subgroup was injected with TC1 lung carcinoma cells in the left flank after 2 weeks of IH. Exosomes from mouse plasma and from 10 adult human patients with OSA before and after treatment for 6 weeks were cocultured with mouse TC1 and human adenocarcinoma cells lines. Malignant tumor properties such as proliferation, migration, invasion, and endothelial monolayer disruption were assessed, as was micro-RNA (miRNA), exosomal content, and transcriptomic effects of exosomes on TC1 cells in vitro to identify target genes.
  
  
  RESULTS
  Application of IH-induced exosomes from either IH-exposed tumor-bearing (IH+) or non-tumor-bearing (IH-) mice significantly promoted TC1 malignant properties. Similarly, before adherent treatment, exosomes from patients with OSA significantly enhanced proliferation and migration of human adenocarcinoma cells compared with after adherent treatment. Eleven distinct miRNAs emerged in IH-exposed mice, and their gene targets in TC1 cells were identified.
  
  
  CONCLUSIONS
  Circulating exosomes released under IH conditions in vivo selectively enhance specific properties of lung tumor cell cultures. Thus, plasma exosomes participate in the increased tumor aggressiveness observed in patients with OSA.
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-IDIBAPS, Barcelona, Spain; CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors: Isaac
authors: I
authors: Almendros
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors: Abdelnaby
authors: A
authors: Khalyfa
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors: Wojciech
authors: W
authors: Trzepizur
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors: Alex
authors: A
authors: Gileles-Hillel
authors: Center for Research Informatics, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors: Lei
authors: L
authors: Huang
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors: Mahzad
authors: M
authors: Akbarpour
authors: Center for Research Informatics, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors: Jorge
authors: J
authors: Andrade
authors: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-IDIBAPS, Barcelona, Spain; CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors: Ramon
authors: R
authors: Farré
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL. Electronic address: dgozal@uchicago.edu.
authors: David
authors: D
authors: Gozal
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D017286:Polysomnography; D011897:Random Allocation; D012891:Sleep Apnea Syndromes / Q000150:complications*; D046888:Tissue Array Analysis
chemical_list: D035683:MicroRNAs
keywords: OSA; cancer; exosome cargo; exosomes; extracellular vesicles; intermittent hypoxia; mRNA; miRNA; microenvironment