Abstract
Recent epidemiological studies provide strong evidence suggesting obesity is a risk factor in several cancers, including breast cancer. However, the exact molecular mechanisms by which obesity increases the risk of breast cancer are poorly understood. In this study, we evaluated the effect of diet-induced obesity on breast carcinogenesis in the MMTV-PyMT breast cancer model. Four-week old, female mice (n = 40) were randomized to high fat (HFD) or low fat (LFD) diets for 8 weeks. Body weights were obtained weekly and mice were imaged for mammary tumor volumes by 3D ultrasound. Tumor burden was collected during early and late stages, weighed and fixed for immunohistochemical staining. Blood and tissue from the liver, lung, and mesenteric fat were also collected. We also compared the basal VEGF protein expression in skeletal muscle, adipose tissue and mammary tumors from MMTV-PyMT mice and compared these levels against background nontransgenic FVB/N mice. Average tumor volumes and tumor burdens were markedly greater in the mice fed HFD than in LFD and showed an increased number of metastases to the lung by 2-fold. HFD increased mammary cell proliferation and elevated Chemokine (C-C motif) ligand 2 (CCL2) in the blood, tumor beds and adipose tissue. Histopathological analysis showed more tumor-associated macrophages and increased microvessel density with diet-induced obesity. Significantly more crown-like structures were evident in adipose tissue from obese mice at both early and late stage carcinoma. Adipose tissue of MMTV-PyMT mice exhibited greater VEGF protein expression compared to adipose tissue of control FVB mice, and greater VEGF protein compared to tumor VEGF expression. Our findings demonstrate that diet-induced obesity exacerbates breast cancer progression in MMTV-PyMT mice and suggests that high body adiposity caused by diet-induced changes promotes an inflammatory and angiogenic phenotype in breast cancer. NIH P20 RR016440, P30 R032138 and GM103488, and P20 RR016477.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-01-01.
Volume 73, Issue 24 Supplement
