Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression

Abstract

Obese postmenopausal women have 50% higher risk of breast cancer than non-obese women. There is no animal model that mimics postmenopausal obesity related to breast cancer progression. This study used age-relevant C57BL/6 mice for determing whether postmenopausal obesity increases VEGF expression, tumor angiogenesis, and breast tumor growth. Ovariectomy (OVX) was performed in 12 sixty week-old female mice, then followed by a low fat (5%, LF, n=6) or a high-fat (60%, HF, n=6) diet for 12 weeks. In the 8th wk of the dietary program, 10^6 E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland, and tumor size was monitored for 4 wk. OVX/HF mice significantly increased body weight (55.3±1.7 vs. 41.5±1.5 g), visceral fat/BW ratio (0.062±0.005 vs. 0.032±0.003), tumor weight (4.62±0.63 vs. 1.98±0.27 g), plasma VEGF levels (69±7.1 vs. 48±3.5 pg/ml), visceral fat VEGF levels (424.4±39.5 vs. 208.5±22.4 pg/mg protein), tumor VEGF levels (73.3±3.8 vs. 49.5±4.3 pg/mg protein), and intratumoral microvessel density (173±3.7 vs. 139±4.3 IM#/mm^2), compared to OVX/LF group, respectively (n=6; P<0.01). These findings support the hypothesis that postmenopausal obesity promotes tumor angiogenesis and breast cancer progression, possibly through increased adipose tissue mass and adipokines such as VEGF that could systemically and locally affect breast cancer progression.