Obesity and intermittent hypoxia increase tumor growth ina 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 (40–45 g) and 18 lean (20–25 g)] by injecting 106 B16F10 cells in the flank. Nineteen mice (10 obese/9 lean) were subjected to IH (6 h/day for 17 days). 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 ± 0.32 g. In obese animals, a similar increase in tumor growth (1.94 ± 0.18 g) was observed under normoxia, while adding IH had no further effect (1.69 ± 0.23 g). 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 (q=0.76, p<0.001) in the whole sample; it increased in lean IH-treated animals from 66.40 ± 3.47 to 108.37 ± 9.48 pg/mL, p < 0.001), while the high baseline value in obese mice (106.90 ± 4.32 pg/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.