Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea

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.