title: Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea.
abstract: BACKGROUND
  Intermittent hypoxia and obesity which are two pathological conditions commonly found in patients with obstructive sleep apnea (OSA), potentially enhance cancer progression.
  
  
  OBJECTIVE
  To investigate whether obesity and/or intermittent hypoxia (IH) mimicking OSA affect tumor growth.
  
  
  METHODS
  A subcutaneous melanoma was induced in 40 mice [22 obese (40-45g) and 18 lean (20-25g)] by injecting 10(6) B16F10 cells in the flank. Nineteen mice (10 obese/9 lean) were subjected to IH (6h/day for 17days). A group of 21 mice (12 obese/9 lean) were kept under normoxia. At day 17, tumors were excised, weighed and processed to quantify necrosis and endothelial expression of vascular endothelial growth factor (VEGF) and CD-31. VEGF in plasma was also assessed.
  
  
  RESULTS
  In lean animals, IH enhanced tumor growth from 0.81±0.17 to 1.95±0.32g. In obese animals, a similar increase in tumor growth (1.94±0.18g) was observed under normoxia, while adding IH had no further effect (1.69±0.23g). IH only promoted an increase in tumoral necrosis in lean animals. However, obesity under normoxic conditions increased necrosis, VEGF and CD-31 expression in tumoral tissue. Plasma VEGF strongly correlated with tumor weight (ρ=0.76, p<0.001) in the whole sample; it increased in lean IH-treated animals from 66.40±3.47 to 108.37±9.48pg/mL, p<0.001), while the high baseline value in obese mice (106.90±4.32pg/mL) was unaffected by IH.
  
  
  CONCLUSIONS
  Obesity and IH increased tumor growth, but did not appear to exert any synergistic effects. Circulating VEGF appeared as a crucial mediator of tumor growth in both situations.
authors.affiliation: CIBER de Enfermedades Respiratorias, Servei Pneumologia, Hospital Clínic, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.forename: Josep M
authors.initials: JM
authors.lastname: Montserrat
authors.forename: Marta
authors.initials: M
authors.lastname: Torres
authors.forename: Maria R
authors.initials: MR
authors.lastname: Bonsignore
authors.forename: Laura
authors.initials: L
authors.lastname: Chimenti
authors.forename: Daniel
authors.initials: D
authors.lastname: Navajas
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000860:Hypoxia / Q000150:complications*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009368:Neoplasm Transplantation / Q000473:pathology*; D009765:Obesity / Q000150:complications*; D012891:Sleep Apnea Syndromes / Q000150:complications*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042461:Vascular Endothelial Growth Factor A