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HYPOXIA AS A MEDIATOR OF ADIPOKINE PRODUCTION IN PATIENTS AT RISK FOR BREAST CANCER
Presenter: Irene Pien, BA, BS
Co-Authors: Fisher M; Bond J; Lem S; Frye E; Suarez A; Ibarra-Drendall C; Klitzman B; Seewladt V; Hollenbeck ST
Duke University Medical Center

Purpose: Obesity is associated with an increased risk of breast cancer. Evidence suggests that cytokines secreted by adipose tissue (adipokines) may promote breast cancer. Adipose tissue responds to hypoxia by secreting pro-inflammatory adipokines. We evaluated serum adipokines in relation to body mass index (BMI) in patients at risk for breast cancer and then tested the hypothesis that hypoxia acts as a mediator for altering adipokine release.

Methods: Peripheral blood was drawn from 74 women followed in our high-risk breast clinic. Serum was evaluated using ELISA to quantify adipokine levels and this was correlated with BMI. Human preadipocytes (PA), mature adipocytes (MA) and dermal fibroblasts (DF) were kept in either normal or low oxygen (0.5% O2) conditions for 48 hours to generate conditioned media. Soluble IL6, Adiponectin (Adp) and Leptin (Lp) were quantified using ELISA.

Results: Serum IL6 and Adp did not correlate with BMI. However, elevated serum Lp was associated with the presence of obesity (p<0.05) in our patient population (Fig 1A). At both normal and low oxygen, conditioned media from PA s contained more IL-6 than conditioned media from MA s and/or DF s (p<0.05). Hypoxia resulted in a decrease in soluble IL6 from PA conditioned media (0.7-fold) and an increase in soluble IL6 from MA conditioned media (2.9-fold). At both normal and low oxygen conditions, MA s produced significantly more soluble Adp and Lp than PA s and DF s (p<0.05). In MA s, hypoxia decreased soluble Adp (24-fold) and increased soluble Lp levels (1.3-fold) (Fig 1B). Next, we evaluated the effect of BMI on MA Lp production. In normal oxygen, media from MA s from high BMI donors contained 3.1-fold more Lp than media from MA s from low BMI donors (p<0.05). Hypoxia increased soluble Lp in media from MA s from both high and low BMI donors (2.0-fold and 5.5-fold).

Conclusion: Serum leptin is elevated in obese patients. Mature adipocytes are a powerful source of leptin production and this may be enhanced by obesity and hypoxia. Targeting obesity and adipokine production may be a valuable approach to prevent breast cancer.


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