Obesity and intermittent hypoxia increase tumor growth ina mouse model of sleep apnea.

Maria Rosaria Bonsignore, Daniel Navajas, Josep M. Montserrat, Laura Chimenti, Ramon Farré, Marta Torres, Isaac Almendros

Risultato della ricerca: Articlepeer review

77 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)1254-1260
Numero di pagine7
RivistaSleep Medicine
Volume13
Stato di pubblicazionePublished - 2012

All Science Journal Classification (ASJC) codes

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